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1.
Indian J Pharmacol ; 56(4): 260-267, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39250623

RESUMEN

OBJECTIVE: Liver derangement underlies the development of metabolic syndrome in perimenopause. Previously, we have observed that durva swaras (DS) improved metabolic-associated fatty liver disease (MAFLD) and abnormal liver enzymes (aspartate aminotransferase and alanine aminotransferase) along with other complications of menopause in ovariectomized rats. We aimed to decipher the hepatoprotective mechanisms of DS in acetaminophen (APAP)-induced liver injury model, which is analogous to the pathophysiology of MAFLD. MATERIALS AND METHODS: Male Swiss albino mice were distributed into three groups at random. Group I (Control) was administered with vehicle (distilled water) for 7 days. Group II (APAP) received vehicle for the first 6 days and APAP (350 mg/kg - single dose) on the 7th day. Group III (APAP + D) received test compound DS (quality complied) at a dose of 133 mg/kg for 6 days and APAP (350 mg/kg - single dose) on the 7th day. Subsequently, blood and liver tissues were subjected to biochemical, ultrastructural, and gene expression analysis. RESULTS: DS pretreatment protected the liver from APAP-induced disruption of sinusoids and necrosis. DS prevented the elevation of liver enzymes - AST and ALT induced by APAP. Importantly, DS inhibited the APAP-elicited increase in messenger ribonucleic acid levels of hepatic nuclear factor-kappa beta (NF-κB) and pro-inflammatory cytokines, namely interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha. Moreover, DS activated gene expression of nuclear factor erythroid 2-related factor 2 and liver-X-receptor-alpha (LXR-α) to combat the liver damage. CONCLUSION: DS hinders APAP-induced liver damage by activating LXR-α and inhibiting the NF-κB-associated pro-inflammatory cytokine gene expression. These observations confirm the protective role of DS in metabolic dysfunction-associated liver conditions.


Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Masculino , Ratones , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Acetaminofén/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Modelos Animales de Enfermedad , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Biomarcadores/sangre , Alanina Transaminasa/sangre , FN-kappa B/metabolismo , Citocinas/metabolismo , Aspartato Aminotransferasas/sangre , Inflamación/tratamiento farmacológico
2.
Medicine (Baltimore) ; 103(36): e39393, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252303

RESUMEN

The community population based studies on the relationship between obstructive sleep apnea and liver injury are limited. The study aimed to clarify the association between sleep apnea (SA) and liver injury by using the data in The National Health and Nutrition Examination Survey. SA was assessed by the sleep questionnaire and liver injury was evaluated by liver function test, hepatic steatosis index, and fibrosis-4. Weighted multivariable linear regression was performed to examine the association between SA and liver injury. Subgroup analyses and sensitivity analysis were also conducted. A total of 19,362 eligible participants were included in the study. After adjusting for confounders, the presence of SA was significantly associated with increased levels of lnALT, lnAST/alanine aminotransferase, lnGGT, and lnHSI (all P values < .05), but not with lnFIB-4 (P > .05). There is a dose-response relationship between the severity of SA and increased levels of lnALT, lnGGT, and decreased levels of lnAST/alanine aminotransferase (test for trend, all P values < .05). Subgroup analyses revealed that the positive association between SA and liver function, liver steatosis showed a tendency to exist in nonobese, younger, non-Hispanic Black, and male populations. Sensitive analysis showed the relationship between SA and liver injury was stable. Self-reported SA was independently associated with elevated liver enzymes and liver steatosis among US population. The association was more pronounced among nonobese, younger, non-Hispanic Black, and male populations.


Asunto(s)
Biomarcadores , Encuestas Nutricionales , Autoinforme , Humanos , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Adulto , Síndromes de la Apnea del Sueño/sangre , Síndromes de la Apnea del Sueño/epidemiología , Alanina Transaminasa/sangre , Pruebas de Función Hepática/métodos , Estados Unidos/epidemiología , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Estudios Transversales , Hígado/lesiones
3.
Bol Med Hosp Infant Mex ; 81(4): 225-231, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39236671

RESUMEN

BACKGROUND: Elevated liver enzyme levels have been associated with metabolic syndrome in both obese and non-obese pediatric populations. This study aims to compare the serum liver enzyme levels in obese adolescents with and without insulin resistance (IR). METHODS: A cross-sectional analysis was conducted involving obese adolescents aged 10-18. We assessed somatometry, serum insulin levels, lipid profiles, and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transferase [GGT]). Statistical differences between groups were evaluated using Student's t-test or the Chi-squared test, with IR (wIR) status matched by propensity scores based on body mass index (BMI) z-scores. RESULTS: The study included 365 adolescents with obesity, 229 wIR, and 136 without (woIR). Before matching, the wIR group had a significantly higher BMI z-score (2.21 vs. 2.14, p = 0.032). After matching for BMI z-scores (n = 122 each group), the wIR group displayed significantly higher levels of AST (32.3 vs. 24.7, p < 0.001) and ALT (42.4 vs. 30.9, p < 0.001), but no significant differences were observed in GGT levels (37.4 vs. 32.5, p = 0.855). CONCLUSION: Obese adolescent's wIR exhibit higher serum ALT and AST levels, suggesting that altered AST is a potential risk factor for IR.


INTRODUCCIÓN: Se ha observado asociación entre niveles elevados de enzimas hepáticas y síndrome metabólico en población pediátrica con y sin obesidad. El objetivo del estudio fue comparar los niveles séricos de enzimas hepáticas entre adolescentes con obesidad con y sin resistencia a la insulina (RI). MÉTODOS: Se realizó un estudio transversal en adolescentes con obesidad entre 10 y 18 años. Se analizaron los datos somatometricos, insulina sérica, perfil lipídico y niveles de enzimas hepáticas (aspartato aminotransferasa [AST], alanina aminotransferasa [ALT] y gamma-glutamil transferasa [GGT]). Análisis estadístico: se utilizó t de Student o la prueba de Chi-cuadrado para evaluar diferencias entre grupos. Los pacientes con RI se emparejaron con pacientes sin RI utilizando puntuaciones de propensión basadas en la puntuación z del IMC. RESULTADOS: Se incluyeron un total de 365 adolescentes con obesidad (229 con RI y 136 sin RI). El grupo con RI tuvo un IMC mayor (con RI 2.21 vs sin RI 2.14 p = 0.032). Después de emparejar los grupos según el IMCz (n = 122 por grupo), el grupo con RI tuvo niveles de AST (24.7 vs., 32.3, p < 0.001) y ALT (30.9 vs., 42.4, p < 0.001) significativamente más altos en comparación al grupo sin RI. Sin embargo, no hubo diferencia en los niveles de GTT (37.4 vs 32.5, p = 0.855). CONCLUSIONES: Los niveles séricos de ALT y AST en adolescents con obesidad y RI fueron mayores. La AST alterada fue un factor de riesgo para presentar RI.


Asunto(s)
Alanina Transaminasa , Aspartato Aminotransferasas , Índice de Masa Corporal , Resistencia a la Insulina , Hígado , Obesidad Infantil , Puntaje de Propensión , gamma-Glutamiltransferasa , Humanos , Adolescente , Estudios Transversales , Femenino , Masculino , Alanina Transaminasa/sangre , Niño , Aspartato Aminotransferasas/sangre , gamma-Glutamiltransferasa/sangre , Hígado/enzimología , Síndrome Metabólico/sangre , Insulina/sangre
4.
Narra J ; 4(2): e799, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39280321

RESUMEN

Monosodium glutamate (MSG) is commonly used as a flavor-enhancing agent in foods, and studies have demonstrated its toxic effects in animal models. Black garlic is known for its antioxidant and anti-inflammatory properties; however, there is a lack of studies on the potential hepatoprotective effect of black garlic ethanol extract (BGE) against MSG-induced hepatotoxicity in rats. The aim of this study was to investigate the hepatoprotective effects of ethanol extract of black garlic against MSG-induced liver damage in animal model. Twenty-five male Wistar rats were randomly assigned to five groups (n=5): negative control, MSG only, and MSG with three different doses of BGE. The MSG only and MSG with BGE groups were orally administered with 8 mg/kg MSG daily. After MSG treatment, the MSG with BGE groups received BGE orally at daily doses of 200, 400, or 600 mg/kg body weight for 16 consecutive days. Subsequently, the levels of serum liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2) were measured. Our data indicated that the group treated with 200 mg/kg BGE had significant lower levels of AST and ALT significantly compared to the MSG-only group. The MSG-treated group had higher levels of the inflammatory markers COX-2 and IFN-γ, which were lowered by administration of 200 mg/kg BGE. In contrast, higher doses of BGE led to greater levels of COX-2 and IFN-γ compared to those in the MSG-only group. This study suggested that BGE might have hepatoprotective effects at low dose, potentially mitigating MSG-induced liver damage. However, the higher dose of black garlic extract did not alleviate inflammation, as shown by the higher levels of COX-2 and IFN-γ.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Ajo , Extractos Vegetales , Ratas Wistar , Glutamato de Sodio , Animales , Ajo/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Masculino , Modelos Animales de Enfermedad , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Interferón gamma/metabolismo , Ciclooxigenasa 2/metabolismo
5.
BMC Med ; 22(1): 397, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285414

RESUMEN

BACKGROUND: The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia-reperfusion injury (HIRI). METHODS: Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. RESULTS: There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161-777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58-366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) µmol/L, P < 0.001 (95% CI: 3.0-8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) µmol/L, P = 0.02 (95% CI: 0.0-5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038). CONCLUSIONS: Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations.


Asunto(s)
Desflurano , Isoflurano , Riñón , Trasplante de Hígado , Hígado , Propofol , Humanos , Propofol/administración & dosificación , Propofol/efectos adversos , Trasplante de Hígado/efectos adversos , Desflurano/administración & dosificación , Lactante , Masculino , Femenino , Isoflurano/análogos & derivados , Isoflurano/administración & dosificación , Isoflurano/efectos adversos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , Donadores Vivos , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Creatinina/sangre , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Pruebas de Función Hepática , Periodo Posoperatorio , Pruebas de Función Renal , Atresia Biliar/cirugía
6.
Lipids Health Dis ; 23(1): 295, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267040

RESUMEN

BACKGROUND: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population. METHODS: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence. RESULTS: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and - 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles. CONCLUSIONS: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs.


Asunto(s)
Alanina Transaminasa , Aspartato Aminotransferasas , Glucemia , Ayuno , Triglicéridos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Alanina Transaminasa/sangre , Adulto , Glucemia/metabolismo , Ayuno/sangre , Anciano , Adolescente , Triglicéridos/sangre , Estudios Transversales , Anciano de 80 o más Años , Aspartato Aminotransferasas/sangre , Adulto Joven , Lípidos/sangre , HDL-Colesterol/sangre
7.
Sci Rep ; 14(1): 20588, 2024 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232127

RESUMEN

Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride-glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (ß 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (ß -0.57, 95% CI -1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature.


Asunto(s)
Alanina Transaminasa , Glucemia , Estatura , Triglicéridos , Humanos , Alanina Transaminasa/sangre , Niño , Femenino , Masculino , Triglicéridos/sangre , Glucemia/análisis , Glucemia/metabolismo , Adolescente , Resistencia a la Insulina
8.
Front Endocrinol (Lausanne) ; 15: 1457598, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253584

RESUMEN

Background: The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population. Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD. Results: Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302. A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters. Conclusion: A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.


Asunto(s)
Alanina Transaminasa , Aspartato Aminotransferasas , Biomarcadores , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/sangre , Masculino , Femenino , Estudios Transversales , Alanina Transaminasa/sangre , Persona de Mediana Edad , Adulto , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Estados Unidos/epidemiología , Índice de Severidad de la Enfermedad , Factores de Riesgo , Adulto Joven , Cirrosis Hepática/epidemiología , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Prevalencia , Anciano , Adolescente
9.
Medicine (Baltimore) ; 103(36): e39437, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252286

RESUMEN

This study aimed to develop and validate a clinical model for predicting the risk of nonalcoholic fatty liver disease (NAFLD) by using data from a cross-sectional study. This investigation utilized data from the Dryad database and employed multivariable logistic regression analysis, restricted cubic spline, and nomogram analysis to achieve comprehensive insights. The discrimination and calibration of the nomogram were evaluated using the receiver operating characteristic curve and calibration plot. A total of 1072 patients were included in the study, including 456 with non-NAFLD and 616 with NAFLD. Significant differences were observed in terms of sex, body mass index (BMI), tobacco, hypertension, diabetes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST ratio, uric acid (UA), fasting blood glucose (FBG), triglyceride (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, and diastolic blood pressure (P < .05 for all comparisons). Multivariable logistic regression analysis indicated that sex, BMI, diabetes, ALT/AST ratio, UA, FBG, and TG were associated with an increased risk of NAFLD. Restricted cubic spline indicated a nonlinear relationship between the risk of NAFLD and variables including ALT/AST ratio, FPG, TG, and UA (P for nonlinearity < .01). The variables in the nomogram included BMI, diabetes, ALT/AST ratio, UA, FBG, and TG. The value of area under the curve was 0.790, indicating that the nomogram prediction model exhibited significant discriminatory accuracy. A reliable clinical model for predicting the risk of NAFLD was developed using readily available clinical data. The model can assist clinicians in identifying individuals with an increased risk of NAFLD, enabling early interventions for preventing and managing this prevalent liver disease.


Asunto(s)
Nomogramas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/sangre , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Factores de Riesgo , Medición de Riesgo/métodos , Adulto , Curva ROC , Modelos Logísticos , Índice de Masa Corporal , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Anciano
10.
Cochrane Database Syst Rev ; 8: CD011929, 2024 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136280

RESUMEN

BACKGROUND: The presence and severity of liver fibrosis are important prognostic variables when evaluating people with chronic hepatitis C (CHC). Although liver biopsy remains the reference standard, non-invasive serological markers, such as the four factors (FIB-4) score and the Forns index, can also be used to stage liver fibrosis. OBJECTIVES: To determine the diagnostic accuracy of the FIB-4 score and Forns index in staging liver fibrosis in people with chronic hepatitis C (CHC) virus, using liver biopsy as the reference standard (primary objective). To compare the diagnostic accuracy of these tests for staging liver fibrosis in people with CHC and explore potential sources of heterogeneity (secondary objectives). SEARCH METHODS: We used standard Cochrane search methods for diagnostic accuracy studies (search date: 13 April 2022). SELECTION CRITERIA: We included diagnostic cross-sectional or case-control studies that evaluated the performance of the FIB-4 score, the Forns index, or both, against liver biopsy, in the assessment of liver fibrosis in participants with CHC. We imposed no language restrictions. We excluded studies in which: participants had causes of liver disease besides CHC; participants had successfully been treated for CHC; or the interval between the index test and liver biopsy exceeded six months. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We performed meta-analyses using the bivariate model and calculated summary estimates. We evaluated the performance of both tests for three target conditions: significant fibrosis or worse (METAVIR stage ≥ F2); severe fibrosis or worse (METAVIR stage ≥ F3); and cirrhosis (METAVIR stage F4). We restricted the meta-analysis to studies reporting cut-offs in a specified range (+/-0.15 for FIB-4; +/-0.3 for Forns index) around the original validated cut-offs (1.45 and 3.25 for FIB-4; 4.2 and 6.9 for Forns index). We calculated the percentage of people who would receive an indeterminate result (i.e. above the rule-out threshold but below the rule-in threshold) for each index test/cut-off/target condition combination. MAIN RESULTS: We included 84 studies (with a total of 107,583 participants) from 28 countries, published between 2002 and 2021, in the qualitative synthesis. Of the 84 studies, 82 (98%) were cross-sectional diagnostic accuracy studies with cohort-based sampling, and the remaining two (2%) were case-control studies. All studies were conducted in referral centres. Our main meta-analysis included 62 studies (100,605 participants). Overall, two studies (2%) had low risk of bias, 23 studies (27%) had unclear risk of bias, and 59 studies (73%) had high risk of bias. We judged 13 studies (15%) to have applicability concerns regarding participant selection. FIB-4 score The FIB-4 score's low cut-off (1.45) is designed to rule out people with at least severe fibrosis (≥ F3). Thirty-nine study cohorts (86,907 participants) yielded a summary sensitivity of 81.1% (95% confidence interval (CI) 75.6% to 85.6%), specificity of 62.3% (95% CI 57.4% to 66.9%), and negative likelihood ratio (LR-) of 0.30 (95% CI 0.24 to 0.38). The FIB-4 score's high cut-off (3.25) is designed to rule in people with at least severe fibrosis (≥ F3). Twenty-four study cohorts (81,350 participants) yielded a summary sensitivity of 41.4% (95% CI 33.0% to 50.4%), specificity of 92.6% (95% CI 89.5% to 94.9%), and positive likelihood ratio (LR+) of 5.6 (95% CI 4.4 to 7.1). Using the FIB-4 score to assess severe fibrosis and applying both cut-offs together, 30.9% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the FIB-4 score when used for assessing significant fibrosis (≥ F2) and cirrhosis (F4) in the main review text. Forns index The Forns index's low cut-off (4.2) is designed to rule out people with at least significant fibrosis (≥ F2). Seventeen study cohorts (4354 participants) yielded a summary sensitivity of 84.7% (95% CI 77.9% to 89.7%), specificity of 47.9% (95% CI 38.6% to 57.3%), and LR- of 0.32 (95% CI 0.25 to 0.41). The Forns index's high cut-off (6.9) is designed to rule in people with at least significant fibrosis (≥ F2). Twelve study cohorts (3245 participants) yielded a summary sensitivity of 34.1% (95% CI 26.4% to 42.8%), specificity of 97.3% (95% CI 92.9% to 99.0%), and LR+ of 12.5 (95% CI 5.7 to 27.2). Using the Forns index to assess significant fibrosis and applying both cut-offs together, 44.8% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the Forns index when used for assessing severe fibrosis (≥ F3) and cirrhosis (F4) in the main text. Comparing FIB-4 to Forns index There were insufficient studies to meta-analyse the performance of the Forns index for diagnosing severe fibrosis and cirrhosis. Therefore, comparisons of the two tests' performance were not possible for these target conditions. For diagnosing significant fibrosis and worse, there were no significant differences in their performance when using the high cut-off. The Forns index performed slightly better than FIB-4 when using the low/rule-out cut-off (relative sensitivity 1.12, 95% CI 1.00 to 1.25; P = 0.0573; relative specificity 0.69, 95% CI 0.57 to 0.84; P = 0.002). AUTHORS' CONCLUSIONS: Both the FIB-4 score and the Forns index may be considered for the initial assessment of people with CHC. The FIB-4 score's low cut-off (1.45) can be used to rule out people with at least severe fibrosis (≥ F3) and cirrhosis (F4). The Forns index's high cut-off (6.9) can be used to diagnose people with at least significant fibrosis (≥ F2). We judged most of the included studies to be at unclear or high risk of bias. The overall quality of the body of evidence was low or very low, and more high-quality studies are needed. Our review only captured data from referral centres. Therefore, when generalising our results to a primary care population, the probability of false positives will likely be higher and false negatives will likely be lower. More research is needed in sub-Saharan Africa, since these tests may be of value in such resource-poor settings.


Asunto(s)
Hepatitis C Crónica , Cirrosis Hepática , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Biopsia , Adulto , Índice de Severidad de la Enfermedad , Hígado/patología , Biomarcadores/sangre , Estudios de Casos y Controles , Sesgo , Estudios Transversales , Recuento de Plaquetas , Alanina Transaminasa/sangre , Sensibilidad y Especificidad , Aspartato Aminotransferasas/sangre
11.
Nutrients ; 16(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39203726

RESUMEN

Parenteral nutrition (PN) is a life-sustaining method to provide adequate nutrients to patients unable to receive oral or enteral nutrition. PN typically contains a mixture of macro- and micro-nutrients, although the lipid composition has been identified as a concern for liver disease. Therefore, the study of the intravenous lipid emulsion (ILE) prescribing practices in home-based PN (HPN) patients and whether differing lipid PN alters liver function tests (LFTs) is needed. METHODS: A retrospective study of monthly LFTs from a random sample of 105 adult HPN patients in the U.S. over a 6-month period was conducted. Patients were receiving olive oil/soy oil (n = 53, Clinolipid), mixed ILE (n = 39, SMOF Lipid), soy oil (SO; n = 4, Intralipid), or none (n = 7). LFTs monitored were alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (T Bili). RESULTS: No differences were observed in baseline LFTs across groups (all, p > 0.25, η2 < 0.04), nor were there differences in age, body mass index, days of PN, or mean PN volume (all, p > 0.36, η2 < 0.05). There were no significant interactions between ILE type and time (all p > 0.64, ηp2 < 0.03), no effect of ILE type (all p > 0.60, ηp2 < 0.03), and no effect of time (all p > 0.69, ηp2 < 0.01) in terms of LFTs. Average LFTs over six months were also not different between ILE types (all p > 0.30, η2 < 0.04). CONCLUSION: These findings suggested that patients were mostly prescribed mixed or ILE PN containing more than one lipid source and that differing ILEs in long-term HPN patients did not alter LFTs over a six-month period.


Asunto(s)
Emulsiones Grasas Intravenosas , Pruebas de Función Hepática , Hígado , Aceite de Oliva , Aceite de Soja , Humanos , Estudios Retrospectivos , Emulsiones Grasas Intravenosas/administración & dosificación , Masculino , Femenino , Aceite de Soja/administración & dosificación , Persona de Mediana Edad , Aceite de Oliva/administración & dosificación , Anciano , Hígado/metabolismo , Adulto , Nutrición Parenteral , Bilirrubina/sangre , Fosfolípidos/administración & dosificación , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Nutrición Parenteral en el Domicilio , Pautas de la Práctica en Medicina/estadística & datos numéricos , Emulsiones/administración & dosificación , Fosfatasa Alcalina/sangre , Hepatopatías , Aceites de Pescado , Triglicéridos
12.
Phytomedicine ; 133: 155878, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39121535

RESUMEN

BACKGROUND: Hepatic fibrosis is a reversible pathological phenomenon caused by the abnormal proliferation of connective tissues in the liver for self-repair after persistent liver injury. Among these tissues, the activation status of hepatic stellate cells (HSCs) is crucial. Glycyrrhizic acid (GA) agents have been proven to have excellent anti-fibrosis effects, but their targets are unclear. PURPOSE: To investigate the anti-hepatic fibrosis effect of GA and its target in activated HSCs. METHODS: A mouse model of hepatic fibrosis was prepared with 20 % carbon tetrachloride (CCl4) and GA was administered continuously for 4 weeks. Subsequently, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅲ procollagen peptide (P III P), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (Col Ⅳ) were measured. Liver tissues were subjected to hematoxylin and eosin (HE), Masson, and Sirius red staining and proteome sequencing analysis. Based on LX-2 cells, activity-based protein profiling (ABPP) was used to investigate the potential targets of GA, which was further validated by the cellular thermal shift assay (CETSA), immunofluorescence co-localization, molecular docking, small interfering RNA (siRNA) and western blot (WB) assays. RESULTS: In vivo, GA significantly reduced serum ALT, AST, HA, P III P, Col IV, and LN levels. HE, Masson, and Sirius red staining showed that GA significantly ameliorated hepatic inflammatory response and collagen deposition in CCl4-treated mice. Proteome sequencing results showed that GA mainly regulated glutathione S-transferase family members involved in glutathione metabolism. In vitro, GA significantly inhibited LX-2 cell proliferation and reduced reactive oxygen species accumulation. ABPP suggested that aldo-keto reductase family 7 member A2 (AKR7A2) was the major binding protein of GA in LX-2 cells. CETSA, fluorescence co-localization, molecular docking, and surface plasmon resonance further validated GA binding to AKR7A2. The WB results showed that GA up-regulated AKR7A2 expression both in vitro and in vivo and was corroborated by siRNA experiments. CONCLUSION: GA targeted AKR7A2 in LX-2 cells to defend against sustained oxidative stress injury, thereby inhibiting the proliferation of activated HSCs and reversing hepatic fibrosis.


Asunto(s)
Tetracloruro de Carbono , Ácido Glicirrínico , Células Estrelladas Hepáticas , Cirrosis Hepática , Estrés Oxidativo , Animales , Ácido Glicirrínico/farmacología , Estrés Oxidativo/efectos de los fármacos , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Ratones , Masculino , Cirrosis Hepática/tratamiento farmacológico , Humanos , Ratones Endogámicos C57BL , Hígado/efectos de los fármacos , Línea Celular , Alanina Transaminasa/sangre , Simulación del Acoplamiento Molecular , Modelos Animales de Enfermedad , Aspartato Aminotransferasas/sangre
13.
Am J Case Rep ; 25: e944508, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39182163

RESUMEN

BACKGROUND Common causes of severely elevated transaminases, especially alanine transaminase, due to liver diseases include drug-induced liver injury and acute viral hepatitis, especially hepatitis E, which can present similarly in clinical practice. Broad differential diagnostic workup in patients with elevated transaminases is required to not overlook the possibility of hepatitis E infection. CASE REPORT We report on a 65-year-old asymptomatic man who was referred to the Emergency Department from the rehabilitation center due to markedly elevated liver transaminases. Physical examination revealed no jaundice or abdominal pain. Laboratory findings included severely elevated aspartate transaminase, alanine transaminase, and bilirubin levels. He was previously treated with imipenem/cilastatin and clindamycin for a surgical site infection of his jaw after the removal of a squamous cell carcinoma 2 weeks earlier. An ultrasound of the liver was unremarkable. Drug-induced liver injury was suspected, and all potentially hepatotoxic drugs, including antibiotics, were stopped. Due to the rapid and marked increase in liver transaminases, further tests were performed, including testing for hepatitis E. Serum anti-hepatitis E virus immunoglobulin M, immunoglobulin G antibodies, and hepatitis E virus-ribonucleic acid-polymerase chain reaction turned positive, and the diagnosis of hepatitis E was confirmed. Supportive care was applied. Liver transaminases decreased spontaneously. CONCLUSIONS The diagnostic workup in patients with markedly elevated liver transaminases and suspected drug-induced liver injury should include the screening for hepatitis E. Making the correct diagnosis is crucial given the differing treatment approaches, the implications on further therapy, and the risk of contagion of hepatitis E.


Asunto(s)
Antibacterianos , Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatitis E , Humanos , Masculino , Anciano , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Hepatitis E/diagnóstico , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Errores Diagnósticos , Clindamicina/efectos adversos , Clindamicina/uso terapéutico , Combinación Cilastatina e Imipenem , Alanina Transaminasa/sangre
14.
Int Immunopharmacol ; 140: 112848, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39096876

RESUMEN

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a serious human health threat given its high morbidity and mortality. Timely and effective antiviral treatment can postpone liver disease progression and reduce the occurrence of HBV-related end-stage liver disease. At present, the antiviral treatment criteria are mainly based on alanine transaminase (ALT) levels, HBV DNA levels and HBV e antigen levels according to the American Association for the Study of Liver Diseases treatment guidelines. However, some chronic hepatitis B (CHB) patients not meeting the above criteria still experience liver disease progression without antiviral treatment. It is urgent to identify a more comprehensive tool to screen out more antiviral treatment candidates as soon as possible. METHODS: Considering the vital role of the immune response in the development of HBV infection and CHB cure, we collected data from 335 treatment-naïve CHB patients and comprehensively analysed their clinical and immune traits (including innate and adaptive responses). The immune parameters were obtained by flow cytometry. Finally, we established a model that can better distinguished CHB patients who need treatment through machine learning and LASSO regression of serological and immune parameters. RESULTS: Through a series of analyses, we selected four important clinical parameters (ALT, HBV DNA, the Fibroscan value, and the A/G ratio) and four immune indicators (NKbright + NKp44+, NKbright + NKG2A+, NKT+GranzymeB+, and CD3 + CD107a + ) from more than 200 variables and then successfully established a mathematical model with high sensitivity and specificity to better screen out antiviral treatment candidates from all CHB patients. CONCLUSIONS: Our results developed a refined model to better screen out antiviral treatment candidates from all CHB patients by combining common clinical parameters and important immune indicators, including innate and adaptive immunity. These findings provide more information for improving treatment guidelines and have potential implications for the timing of antiviral therapy to achieve better virus control and reduce the occurrence of end-stage liver disease.


Asunto(s)
Antivirales , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Antivirales/uso terapéutico , Masculino , Femenino , Adulto , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Persona de Mediana Edad , ADN Viral/sangre , Aprendizaje Automático , Inmunidad Innata/efectos de los fármacos , Alanina Transaminasa/sangre , Inmunidad Adaptativa/efectos de los fármacos
15.
Bull Exp Biol Med ; 177(2): 181-184, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39090467

RESUMEN

We performed a comprehensive study of protein (total protein, medium-molecular-weight peptides, creatinine, and urea), purine (uric acid), and lipid (cholesterol, triglycerides) metabolism, activity of AST, ALT, and acid phosphatase in blood plasma of white male rats under conditions of restriction of motor activity up to 28 days. Patterns of changes in metabolic profile during hypokinesia were established: prevalence of catabolic processes and atherogenic shifts in the lipid spectrum with maximum manifestation on 14-21 days of the experiment.


Asunto(s)
Colesterol , Triglicéridos , Animales , Masculino , Ratas , Triglicéridos/sangre , Triglicéridos/metabolismo , Colesterol/sangre , Colesterol/metabolismo , Ácido Úrico/sangre , Ácido Úrico/metabolismo , Actividad Motora/fisiología , Metaboloma/fisiología , Metabolismo de los Lípidos/fisiología , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Creatinina/sangre , Fosfatasa Ácida/metabolismo , Fosfatasa Ácida/sangre , Urea/sangre , Hipocinesia/metabolismo , Hipocinesia/fisiopatología
16.
Medicine (Baltimore) ; 103(32): e39248, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39121258

RESUMEN

Gastroesophageal reflux disease (GERD) is a common condition worldwide. Despite numerous studies on GERD, the causal relationships between blood/urine metabolites and GERD remain unclear. This study aims to explore the causal relationships between GERD and 35 blood/urine metabolites. In this study, we conducted Mendelian randomization (MR) analyses for 35 blood/urine metabolites with GERD phenotypes from the FinnGen R10 and UKB databases separately. We then performed a meta-analysis of the inverse variance weighted results from the 2 MR analyses and applied multiple corrections to the significant P values from the meta-analysis. Finally, we conducted reverse causality validation for the corrected positive blood/urine metabolite phenotypes with GERD. After conducting MR analysis combined with meta-analysis and performing multiple corrections, we found significant positive causal associations between only 3 blood/urine metabolites and GERD, with no significant reverse associations. Among them, 2 are risk factors for the occurrence of GERD: alanine aminotransferase levels (odds ratio (OR) = 1.120, 95% confidence interval (CI) = 1.064-1.180, P = .0005) and urate levels (OR = 1.095, 95% CI = 1.044-1.147, P = .005). Additionally, sex hormone-binding globulin levels are protective against GERD (OR = 0.928, 95% CI = 0.896-0.961, P = .0009). Elevated levels of the metabolites alanine aminotransferase and urate are associated with an increased risk of GERD, identifying them as risk factors for the condition. In contrast, higher levels of SHBG are linked to a decreased risk of GERD, indicating that SHBG is a protective factor against the disease.


Asunto(s)
Reflujo Gastroesofágico , Análisis de la Aleatorización Mendeliana , Ácido Úrico , Humanos , Reflujo Gastroesofágico/sangre , Ácido Úrico/sangre , Globulina de Unión a Hormona Sexual/análisis , Globulina de Unión a Hormona Sexual/metabolismo , Factores de Riesgo , Alanina Transaminasa/sangre , Biomarcadores/sangre , Fenotipo
17.
Clin Ther ; 46(9): e6-e14, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39097520

RESUMEN

PURPOSE: Even though various randomized controlled trials (RCTs) have assessed the effect of propolis on glycemic indices and liver enzyme concentrations in adults, results have been inconsistent, without conclusive evidence. This systematic review and meta-analysis of RCTs sought to evaluate the effects of propolis consumption on glycemic indices and liver enzymes, fasting blood glucose, insulin, homeostatic model assessment of insulin resistance, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase in adults. METHODS: Two independent researchers systematically searched PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library for English-language RCTs published up to April 2024. The results were generated through a random-effects model and presented as the weighted mean difference (WMD) with a 95% CI. The Cochrane Risk of Bias Tool for RCTs and Grading of Recommendations Assessment, Development, and Evaluation assessment were used to evaluate quality assessment and certainty of evidence. FINDINGS: A total of 21 RCTs were included. A pooled analysis of 24 trials reported that propolis consumption led to a significant reduction in fasting blood glucose (WMD, -9.75 mg/dL; 95% CI, -16.14 to -3.35), insulin (WMD, -1.64 µU/mL; 95% CI, -2.61 to -0.68), glycosylated hemoglobin (WMD, -0.46%; 95% CI, -0.71 to -0.21), homeostatic model assessment of insulin resistance (WMD, -0.54; 95% CI, -0.98 to -0.09), alanine transaminase (WMD, -2.60 IU/L; 95% CI, -4.58 to -0.61), and aspartate aminotransferase (WMD, -2.07 IU/L; 95% CI, -3.05 to -1.09). However, there were no significant effects on gamma-glutamyl transferase in comparison with the control group. IMPLICATIONS: This meta-analysis has shown that propolis supplementation may have beneficial effects on glycemic indices and liver enzymes. Future high-quality, long-term RCTs are needed to confirm our results. CLINICALTRIALS: gov identifiers: CRD42024524763. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.


Asunto(s)
Glucemia , Índice Glucémico , Hígado , Própolis , Humanos , Própolis/administración & dosificación , Hígado/efectos de los fármacos , Hígado/enzimología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Adulto , Índice Glucémico/efectos de los fármacos , Resistencia a la Insulina , Aspartato Aminotransferasas/sangre , Insulina , Ensayos Clínicos Controlados Aleatorios como Asunto , Alanina Transaminasa/sangre , Hemoglobina Glucada/metabolismo , gamma-Glutamiltransferasa/sangre , Relación Dosis-Respuesta a Droga
18.
Toxicol Lett ; 400: 16-23, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39096942

RESUMEN

Diacylglycerol O-acyltransferase 1 (DGAT1) is a key enzyme for fat absorption step in the enterocytes. We previously reported that DGAT1 inhibition increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in corn oil-loaded rats via protein kinase C (PKC) activation. In the present study, we investigated the mechanism with respect to the morphology and permeability of the small intestine, focusing on PKC function, and found that shortening of the intestinal villi and a decrease in the number of tdT-mediated dUTP-biotin nick-end labeling-positive cells in the tips of the villi were observed in the jejunum of DGAT1 inhibitor-treated rats loaded with corn oil. These results suggested that the tips of the villi were shed into the intestinal lumen. Next, fluorescein isothiocyanate-dextran, 110 kDa (FD-110) was administered intraduodenally to DGAT1 inhibitor-treated rats loaded with corn oil and we found that plasma FD-110 concentrations increased, indicating that the intestinal permeability to molecules with a molecular weight of approximately 110,000 (e.g., ALT and AST) increased. Taken together, the present results suggested that DGAT1 inhibitor-treatment in combination with corn oil causes ALT and AST to leak from the enterocytes into the blood by shedding the tips of the intestinal villi and increasing intestinal permeability.


Asunto(s)
Alanina Transaminasa , Aspartato Aminotransferasas , Aceite de Maíz , Diacilglicerol O-Acetiltransferasa , Mucosa Intestinal , Permeabilidad , Animales , Alanina Transaminasa/sangre , Masculino , Aspartato Aminotransferasas/sangre , Diacilglicerol O-Acetiltransferasa/antagonistas & inhibidores , Diacilglicerol O-Acetiltransferasa/metabolismo , Permeabilidad/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Ratas , Dextranos , Proteína Quinasa C/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Fluoresceína-5-Isotiocianato/análogos & derivados , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Absorción Intestinal/efectos de los fármacos , Ratas Sprague-Dawley , Ratas Wistar , Funcion de la Barrera Intestinal
19.
Microb Pathog ; 195: 106898, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39208956

RESUMEN

Helicobacter pylori infection has been thought to be associated with liver diseases, although the exact mechanisms remain elusive. This study identified H. pylori-induced liver inflammation and tissue damage in infected mice and examined the exosome-mediated mechanism underlying H. pylori infection's impact on liver injury. Exosomes were isolated from H. pylori-infected gastric epithelial GES-1 cells (Hp-GES-EVs), and the crucial virulence factor CagA was identified within these exosomes. Fluorescent labeling demonstrated that Hp-GES-EVs can be absorbed by liver cells. Treatment with Hp-GES-EVs enhanced the proliferation, migration, and invasion of Hep G2 and Hep 3B cells. Additionally, exposure to Hp-GES-EVs activated NF-κB and PI3K/AKT signaling pathways, which provides a reasonable explanation for the liver inflammation and neoplastic traits. Using a mouse model established via tail vein injection of Hp-GES-EVs, exosome-driven liver injury was evidenced by slight hepatocellular erosion around the central hepatic vein and elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and IL-6. Administering the exosome inhibitor GW4869 via intraperitoneal injection in mice resulted in a reduction of liver damage caused by H. pylori infection. These findings illuminate the exosome-mediated pathogenesis of H. pylori-induced liver injury and offer valuable insights into the extra-gastrointestinal manifestations of H. pylori infection.


Asunto(s)
Antígenos Bacterianos , Proteínas Bacterianas , Modelos Animales de Enfermedad , Exosomas , Infecciones por Helicobacter , Helicobacter pylori , Hígado , Transducción de Señal , Exosomas/metabolismo , Animales , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/patogenicidad , Ratones , Humanos , Proteínas Bacterianas/metabolismo , Hígado/patología , Hígado/metabolismo , Hígado/microbiología , Antígenos Bacterianos/metabolismo , Compuestos de Bencilideno/farmacología , Compuestos de Anilina/farmacología , FN-kappa B/metabolismo , Células Hep G2 , Aspartato Aminotransferasas/sangre , Interleucina-6/metabolismo , Alanina Transaminasa/sangre , Proliferación Celular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Epiteliales/microbiología , Células Epiteliales/metabolismo , Movimiento Celular , Línea Celular , Masculino , Factores de Virulencia/metabolismo
20.
Asian Pac J Cancer Prev ; 25(8): 2919-2928, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-39205591

RESUMEN

The study aimed to investigate the effect of the aqueous extract of the chamomile plant on oxidative stress induced by procyclidine in rats. 30 rats were randomly divided into five groups, with 6 rats in each group. The first group was given distilled water only, while the second group was administered procyclidine (1 mg/kg body weight) in three doses daily for a period of 60 days. The third group was given procyclidine in the same doses as the second group for 30 days. Afterward, they were administered an aqueous extract of chamomile (300 mg/kg) for another 30 days. The fourth group was administered the aqueous extract (300 mg/kg) for 30 days. Subsequently, they were given procyclidine in the same doses as the second group for another 30 days. On the other hand, the fifth group was administered the aqueous extract of chamomile (300 mg/kg) for a period of 60 days to investigate the potential effects of the extract. Afterward, blood samples were drawn to measure various biological parameters, including Total Oxidant Status (TOS), Malondialdehyde (MDA), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Acetylcholinesterase (AChE) activity. Finally, an anatomical study was conducted on the kidneys, brain, and liver to enhance the research. The results displayed a significant increase in the levels of TOS, MDA, AST, ALT enzymes, and Ach-E activity in the second group compared to the first group. Groups 3 and 4 significantly decreased compared to the second group based on the same standards. In regard to Group 5, there are no significant moral differences between it and Group 1. Finally, this study demonstrated the importance of using chamomile extract as an antioxidant and its potential in cancer prevention against the oxidative stress induced by excessive doses of procyclidine. (p ≤ 0.005).


Asunto(s)
Antioxidantes , Manzanilla , Estrés Oxidativo , Extractos Vegetales , Estrés Oxidativo/efectos de los fármacos , Animales , Extractos Vegetales/farmacología , Ratas , Manzanilla/química , Antioxidantes/farmacología , Masculino , Neoplasias/prevención & control , Neoplasias/tratamiento farmacológico , Neoplasias/inducido químicamente , Neoplasias/metabolismo , Malondialdehído/metabolismo , Ratas Wistar , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Alanina Transaminasa/metabolismo , Alanina Transaminasa/sangre
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