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In the present study, we investigated whether curcumin administration would interfere with the main renal features of l-NAME-induced hypertension model. For this purpose, we conducted both in vitro and in vivo experiments to evaluate renal indicators of inflammation, oxidative stress, and metalloproteinases (MMPs) expression/activity. Hypertension was induced by l-NAME (70 mg/kg/day), and Wistar rats from both control and hypertensive groups were treated with curcumin (50 or 100 mg/kg/day; gavage) or vehicle for 14 days. Blood and kidneys were collected to determine serum creatinine levels, histological alterations, oxidative stress, MMPs expression and activity, and ED1 expression. l-NAME increased blood pressure, but both doses of curcumin treatment reduced these values. l-NAME treatment increased creatinine levels, glomeruli area, Bowman's space, kidney MMP-2 activity, as well as MMP-9 and ED1 expression, and reduced the number of glomeruli. Curcumin treatment prevented the increase in creatinine levels, MMP-2 activity, and reduced MMP-2, MMP-9, ED1, and superoxide levels, as well as increased superoxide dismutase activity and partially prevented glomeruli alterations. Moreover, curcumin directly inhibited MMP-2 activity in vitro. Thus, our main findings demonstrate that curcumin reduced l-NAME-induced hypertension and renal glomerular alterations, inhibited MMP-2 and MMP-9 expression/activity, and reduced oxidative stress and inflammatory processes, which may indirectly impact hypertension-induced renal outcomes.
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Curcumina , Hipertensión , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , NG-Nitroarginina Metil Éster , Ratas Wistar , Animales , Curcumina/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Ratas , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Estrés Oxidativo/efectos de los fármacos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/tratamiento farmacológicoRESUMEN
Background: Deposition of adipose tissue may have a promoting role in the development of diabetic complications. This study is aimed at investigating the relationship between adipose tissue thickness and risk of contrast-induced nephropathy (CIN) in patients with Type 2 diabetes mellitus (T2DM). Methods: A total of 603 T2DM patients undergoing percutaneous coronary angiography or angioplasty with suspicious or confirmed stable coronary artery disease were enrolled in this study. The thicknesses of perirenal fat (PRF), subcutaneous fat (SCF), intraperitoneal fat (IPF), and epicardial fat (ECF) were measured by color Doppler ultrasound, respectively. The association of various adipose tissues with CIN was analyzed. Results: Seventy-seven patients (12.8%) developed CIN in this cohort. Patients who developed CIN had significantly thicker PRF (13.7 ± 4.0 mm vs. 8.9 ± 3.6 mm, p < 0.001), slightly thicker IPF (p = 0.046), and similar thicknesses of SCF (p = 0.782) and ECF (p = 0.749) compared to those who did not develop CIN. Correlation analysis showed that only PRF was positively associated with postoperation maximal serum creatinine (sCr) (r = 0.18, p = 0.012), maximal absolute change in sCr (r = 0.33, p < 0.001), and maximal percentage of change in sCr (r = 0.36, p < 0.001). In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of PRF (0.809) for CIN was significantly higher than those of SCF (0.490), IPF (0.594), and ECF (0.512). Multivariate logistic regression analysis further confirmed that thickness of PRF, rather than other adipose tissues, was independently associated with the development of CIN after adjusted for confounding factors (odds ratio (OR) = 1.53, 95% CI: 1.38-1.71, p < 0.001). Conclusions: PRF is independently associated with the development of CIN in T2DM patients undergoing coronary catheterization.
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Medios de Contraste , Angiografía Coronaria , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Medios de Contraste/efectos adversos , Persona de Mediana Edad , Anciano , Angiografía Coronaria/efectos adversos , Factores de Riesgo , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Enfermedades Renales/inducido químicamente , Grasa Intraabdominal/diagnóstico por imagen , Cateterismo Cardíaco/efectos adversos , Creatinina/sangreRESUMEN
OBJECTIVE: To explore the effects of Qingshen Granules (QSG) on adenine-induced renal fibrosis in mice and in uric acid (UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes, miR-330-3p and CREBBP. METHODS: A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks. An adenoassociated virus vector was injected into the tail vein, and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9, Hsp70, and TSG101 and expressions of Col-III, α-SMA, FN, and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining. In the cell experiment, NRK-49F cells were stimulated with uric acid (400 µmol/L) followed by treatment with QSG-medicated serum from SD rats, and the changes in expressions of the exosomal markers and Col-III, α-SMA, FN, and E-cad were analyzed. Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP, whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells. RESULTS: The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9, Hsp70, and TSG101, which were decreased by treatment with QSG. The expressions of Col-III, α-SMA, and FN increased and Ecad decreased in the mouse models but these changes were reversed by QSG treatment. QSG treatment obviously alleviated renal fibrosis in the mouse models. Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p, increased CREBBP levels, and reduced fibrosis in the mouse models. Dual luciferase assay confirmed CREBBP as a target of miR-330-3p, which was consistent with the results of the cell experiments. CONCLUSION: QSG inhibits renal fibrosis in mice by regulating the exosomes, reducing miR-330-3p levels, and increasing CREBBP expression.
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Exosomas , Fibrosis , Riñón , MicroARNs , Animales , Exosomas/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Riñón/patología , Riñón/metabolismo , Proteína de Unión a CREB/metabolismo , Proteína de Unión a CREB/genética , Enfermedades Renales/metabolismo , Enfermedades Renales/inducido químicamente , Medicamentos Herbarios Chinos/farmacología , Adenina , Ratas , Masculino , Ácido Úrico , Línea CelularRESUMEN
Peroxisome proliferator-activated receptor-alpha (PPAR-α) and its exogenous activators (fibrates) promote autophagy. However, whether the deleterious effects of PPAR-α deficiency on doxorubicin (DOX)-induced podocytopathy are associated with reduced autophagy remains to be clarified. We investigated the mechanisms of PPAR-α in DOX-induced podocytopathy and tubular injury in PPAR-α knockout (PAKO) mice and in a murine podocyte cell line. DOX-treated PAKO mice showed higher serum levels of triglycerides and non-esterified fatty acids and more severe podocytopathy than DOX-treated wild-type mice, as evidenced by higher urinary levels of proteins and podocalyxin at 3 days to 2 weeks and higher blood urea nitrogen and serum creatinine levels at 4 weeks. Additionally, there was an increased accumulation of p62, a negative autophagy marker, in the glomerular and tubular regions in DOX-treated PAKO mice at Day 9. Moreover, DOX-treated PAKO mice showed more severe glomerulosclerosis and tubular damage and lower podocalyxin expression in the kidneys than DOX-treated control mice at 4 weeks. Furthermore, DOX treatment increased p-p53, an apoptosis marker, and cleaved the caspase-3 levels and induced apoptosis, which was ameliorated by fenofibrate, a PPAR-α activator. Fenofibrate further enhanced AMPK activation and autophagy under fed and fasting conditions. Conclusively, PPAR-α deficiency enhances DOX-induced podocytopathy, glomerulosclerosis, and tubular injury, possibly by reducing autophagic activity in mouse kidneys.
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Autofagia , Doxorrubicina , Ratones Noqueados , PPAR alfa , Podocitos , Animales , Podocitos/metabolismo , Podocitos/patología , Podocitos/efectos de los fármacos , Doxorrubicina/efectos adversos , PPAR alfa/metabolismo , PPAR alfa/genética , Ratones , Autofagia/efectos de los fármacos , Línea Celular , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/genética , Apoptosis/efectos de los fármacos , Fenofibrato/farmacología , MasculinoRESUMEN
Hexafluoropropylene oxide trimer acid (HFPO-TA) is an emerging environmental pollutant that can accumulate in air and surface water. Currently, it has been widely used in fluoropolymer industry, which could cause serious environmental pollution. Due to the high bioaccumulation, the accumulation of pollutants may have an adverse effect on the normal physiological function of the kidneys. However, the toxic effects of HFPO-TA on the kidney are unknown. In this study, we investigated the toxic effects of HFPO-TA exposure on the rat kidney and its mechanism of action. Male SD rats were divided into 4 groups: control group (Ctrl group), L group (0.125â¯mg/kg/d), M group (0.5â¯mg/kg/d) and H group (2â¯mg/kg/d). After 14 consecutive days of gavage, periodic acidsilver methenamine (PASM) and hematoxylin-eosin (HE) staining were used to examine the structure of the kidneys. We also used transcriptome sequencing (RNA-seq) to identify differentially expressed genes (DEGs) in the testes of rats in both the control and high dose groups. Besides, expression of key proteins was analyzed by immunohistochemistry. The results indicated that HFPO-TA can lead to injured renal capsule, change glomerular shape and have a significant impact on the protein expression levels of AQP2, p-AQP2 and PPARα. Additionally, the level of total cholesterol (TC) was obviously decreased after HFPO-TA exposure. RNA-seq analysis showed that HFPO-TA primarily affected peroxisome proliferator-activated receptor (PPAR) signaling pathway that is associated with lipid metabolism and cyclic adenosine monophosphate (cAMP) signaling pathway. In summary, exposure to HFPO-TA can lead to kidney damage and lipid metabolism disorders.
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Riñón , Metabolismo de los Lípidos , Ratas Sprague-Dawley , Animales , Masculino , Ratas , Riñón/efectos de los fármacos , Riñón/patología , Metabolismo de los Lípidos/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patologíaAsunto(s)
Ácidos Aristolóquicos , Medicamentos Herbarios Chinos , Humanos , Ácidos Aristolóquicos/efectos adversos , Masculino , Lactante , Medicamentos Herbarios Chinos/efectos adversos , Enfermedades Renales/inducido químicamente , Aristolochia/química , Aristolochia/efectos adversos , Riñón/patología , Riñón/efectos de los fármacosRESUMEN
Aristolochic acid nephropathy (AAN) is a rapidly progressive kidney disease caused by medical or environmental exposure to aristolochic acids (AAs). This study aimed to identify serum metabolites associated with the severity of acute AAN and investigate the underlying mechanisms. Male C57BL/6 mice were treated with vehicle and 3 doses of aristolochic acid I (AAI) (1.25, 2.5, and 5â¯mg/kg/d) for 5 days by intraperitoneal injection. The results showed that AAI dose-dependently increased blood urea nitrogen (BUN) and serum creatinine (Scr) levels and renal pathological damage. Non-targeted metabolomics revealed that differences in serum metabolite profiles from controls increased with increasing AAI doses. Compared with the control group, 56 differentially expressed metabolites (DEMs) that could be affected by all 3 doses of AAI were obtained. We further identified 13 DEMs whose abundance significantly correlated with Scr and BUN levels and had good predictive values for diagnosing AAI exposure. Among the 13 DEMs, lipids and lipid-like molecules constituted the majority. Western blotting found that AAI suppressed renal fatty acid oxidation (FAO)-related enzymes expression. In conclusion, these findings provided evidence for developing biomarkers for monitoring AAs exposure and AAN diagnosis and indicated activation of FAO as a potential direction for the treatment of AAN.
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Ácidos Aristolóquicos , Biomarcadores , Ratones Endogámicos C57BL , Ácidos Aristolóquicos/toxicidad , Animales , Masculino , Biomarcadores/sangre , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/sangre , Enfermedades Renales/patología , Nitrógeno de la Urea Sanguínea , Metabolómica , Ratones , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Índice de Severidad de la Enfermedad , Modelos Animales de EnfermedadRESUMEN
Cisplatin (CDDP) often leads to kidney impairment, limiting its effectiveness in cancer treatment. The lack of mitophagy in proximal tubules exacerbates this issue. Hence, targeting SIRT-3 and PGC1-α shows promise in mitigating CDDP-induced kidney damage. The potential renoprotective effects of linagliptin, however, remain poorly understood. This study represents the first exploration of linagliptin's impact on CDDP-induced kidney impairment in rats, emphasizing its potential role in mitophagic pathways. The experiment involved four rat groups: Group (I) received saline only, Group (II) received a single intraperitoneal injection of CDDP at 6 mg/kg. Groups (III) and (IV) received linagliptin at 6 and 10 mg/kg p.o., respectively, seven days before CDDP administration, continuing for an additional four days. Various parameters, including renal function tests, oxidative stress, TNF-α, IL-1ß, IL-6, PGC-1α, FOXO-3a, p-ERK1, and the gene expression of SIRT-3 and P62 in renal tissue, were assessed. Linagliptin improved renal function, increased antioxidant enzyme activity, and decreased IL-1ß, TNF-α, and IL-6 expression. Additionally, linagliptin significantly upregulated PGC-1α and PINK-1/Parkin-2 expression while downregulating P62 expression. Moreover, linagliptin activated FOXO-3a and SIRT-3, suggesting a potential enhancement of mitophagy. Linagliptin demonstrated a positive impact on various factors related to kidney health in the context of CDDP-induced impairment. These findings suggest a potential role for linagliptin in improving cancer treatment outcomes. Clinical trials are warranted to further investigate and validate its efficacy in a clinical setting.
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Cisplatino , Linagliptina , Mitofagia , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Ubiquitina-Proteína Ligasas , Animales , Linagliptina/farmacología , Cisplatino/toxicidad , Mitofagia/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Masculino , Ratas , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Sirtuina 3/metabolismo , Sirtuina 3/genética , Proteínas Quinasas/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Ratas Wistar , Antineoplásicos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , SirtuinasRESUMEN
BACKGROUND: Recent studies have reported that helix B surface polypeptide (HBSP), an erythropoietin derivative, exhibits strong tissue protective effects, independent of erythropoietic effects, in a renal ischemia-reperfusion (IR) injury model. Meanwhile, the transforming growth factor-ß (TGF-ß) superfamily member glial cell line-derived neurotrophic factor (GDNF) demonstrated protective effect on podocytes in vitro. Using a rat puromycin aminonucleoside nephropathy (PAN) model, this study observed the renal protective effect of HBSP and investigated its renal protective effect on podocytes and mechanism related to GDNF. METHODS: Rats nephropathy model was induced by injection of 60 mg/kg of PAN via the tail vein. Rats in the PAN + HBSP group were injected intraperitoneally with HBSP (8 nmol/kg) 4 h before the model was induced, followed by intraperitoneal injections of HBSP once every 24 h for 7 consecutive days. The 24-hour urinary protein level was measured once every other day, and blood and renal tissue samples were collected on the 7th day for the examination of renal function, complete blood count, renal pathological changes and the expression levels of GDNF. RESULTS: Compared with the control group, the PAN nephropathy rat model showed a large amount of urinary protein. The pathological manifestations were mainly extensive fusion and disappearance of foot processes, along with vacuolar degeneration of podocytes and their separation from the glomerular basement membrane. GDNF expression was upregulated. Compared with the PAN + vehicle group, the PAN + HBSP group showed decreased urinary protein (p < 0.05). Pathological examination revealed ameliorated glomerular injury and vacuolar degeneration of podocytes. The expression of GDNF in the PAN nephropathy group was increased, when compared with the control group. The greatest expression of GDNF observed in the PAN + HBSP group (p < 0.05). CONCLUSIONS: The expression of GDNF in the kidney of PAN rat model was increased. HBSP reduced urinary protein, ameliorated pathological changes in renal podocytes, increased the expression of GDNF in the PAN rat model. HBSP is likely to exert its protective effects on podocytes through upregulation of GDNF expression.
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Modelos Animales de Enfermedad , Factor Neurotrófico Derivado de la Línea Celular Glial , Enfermedades Renales , Podocitos , Puromicina Aminonucleósido , Ratas Sprague-Dawley , Animales , Ratas , Podocitos/efectos de los fármacos , Podocitos/patología , Podocitos/metabolismo , Masculino , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Enfermedades Renales/patología , Riñón/patología , Riñón/efectos de los fármacos , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Eritropoyetina , Fragmentos de PéptidosRESUMEN
Although doxorubicin (DOX) is a common chemotherapeutic drug, the serious nephrotoxicity caused by DOX-induced renal fibrosis remains a considerable clinical problem. Tanshinone IIA (Tan IIA), a compound extracted from Salvia miltiorrhiza, has been reported to have an anti-fibrotic effect. Therefore, this study investigated the molecular pathway whereby Tan IIA protects the kidneys from DOX administration. DOX (3 mg/kg body weight) was intraperitoneally administered every 3 d for a total of 7 injections (cumulative dose of 21 mg/kg) to induce nephrotoxicity. Then, Tan IIA (5 or 10 mg/kg/d) was administered by intraperitoneal injection for 28 d. In an in vitro study, 293 T cells were cultured and treated with DOX and Tan IIA for 24 h. Tan IIA reduced the blood urea nitrogen levels elevated by DOX while increasing superoxide dismutase activity, down-regulating reactive oxygen species, ameliorating renal-tubule thickening, and rescuing mitochondrial morphology. Additionally, Tan IIA reduced the renal collagen deposition, increased ATP production and complex-I activity, down-regulated transforming growth factor-ß1 (TGF-ß1) and thrombospondin-1 (TSP-1), and up-regulated sirtuin 3 (SIRT3). Tan IIA significantly increased cell viability. Additionally, RNA interference was employed to silence the expression of SIRT3, which eliminated the effect of Tan IIA in suppressing the expression of TGF-ß1 and TSP-1. In conclusion, Tan IIA ameliorated DOX-induced nephrotoxicity by attenuating oxidative injury and fibrosis. The Tan IIA-induced rescue of mitochondrial morphology and function while alleviating renal fibrosis may be associated with the activation of SIRT3 to suppress the TGF-ß/TSP-1 pathway.
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Abietanos , Fibrosis , Riñón , Estrés Oxidativo , Transducción de Señal , Sirtuina 3 , Trombospondina 1 , Abietanos/farmacología , Abietanos/uso terapéutico , Animales , Estrés Oxidativo/efectos de los fármacos , Sirtuina 3/metabolismo , Humanos , Trombospondina 1/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Doxorrubicina , Enfermedades Renales/inducido químicamente , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Factor de Crecimiento Transformador beta1/metabolismo , Células HEK293 , Factor de Crecimiento Transformador beta/metabolismo , Especies Reactivas de Oxígeno/metabolismo , RatonesRESUMEN
OBJECTIVE: Nowadays, the frequency of complications is also increasing following the increasing frequency of coronary angiography and percutaneous coronary intervention. Contrast-induced nephropathy is one of the most common of these complications. This study aimed to investigate the relationship between the Osaka prognostic score, which has previously been shown to have prognostic importance in gastrointestinal malignancies, and the development of contrast-induced nephropathy. METHODS: The study retrospectively examined the data of 1,498 patients who underwent coronary angiography and percutaneous coronary intervention due to acute coronary syndrome between 2018 and 2023. Demographic characteristics and laboratory findings were retrospectively collected from patients' charts and electronic medical records. RESULTS: Osaka prognostic score (0.84±0.25 vs. 2.2±0.32, p<0.001) was higher in patients who developed contrast-induced nephropathy. Also, Osaka prognostic score [OR 2.161 95%CI (1.101-4.241), p<0.001] was found to be an independent risk factor along with age, diabetes mellitus, systolic pulmonary artery pressure, hemoglobin, hemoglobin, C-reactive protein, albumin, N-terminal brain natriuretic peptide, and systemic immune-inflammation index. The receiver operating characteristic curve showed that the optimal cutoff value of Osaka prognostic score to predict the development of contrast-induced nephropathy was 1.5, with a sensitivity of 83.4 and a specificity of 65.9% [area under the curve: 0.874 (95%CI: 0.850-0.897, p≤0.001)]. CONCLUSION: Osaka prognostic score may be an easily calculable, user-friendly, and useful parameter to predict the development of contrast-induced nephropathy in patients undergoing percutaneous coronary intervention after acute coronary syndromes.
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Medios de Contraste , Angiografía Coronaria , Humanos , Medios de Contraste/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Pronóstico , Angiografía Coronaria/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Síndrome Coronario Agudo/inducido químicamente , Síndrome Coronario Agudo/diagnóstico por imagen , Curva ROC , Medición de Riesgo , Lesión Renal Aguda/inducido químicamente , Enfermedades Renales/inducido químicamente , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Despite accumulating evidence of an association between air pollution and renal disease, studies on the association between long-term exposure to air pollution and renal function are still contradictory. This study aimed to investigate this association in a large population with relatively low exposure and with improved estimation of renal function as well as renal injury biomarkers. METHODS: We performed a cross-sectional analysis in the middle-aged general population participating in the Swedish CardioPulmonary bioImaging Study (SCAPIS; n = 30 154). Individual 10-year exposure to total and locally emitted fine particulate matter (PM2.5), inhalable particulate matter (PM10), and nitrogen oxides (NOx) were modelled using high-resolution dispersion models. Linear regression models were used to estimate associations between exposures and estimated glomerular filtration rate (eGFR, combined creatinine and cystatin C) and serum levels of renal injury biomarkers (KIM-1, MCP-1, IL-6, IL-18, MMP-2, MMP-7, MMP-9, FGF-23, and uric acid), with consideration of potential confounders. RESULTS: Median long-term PM2.5 exposure was 6.2 µg/m3. Almost all participants had a normal renal function and median eGFR was 99.2 mL/min/1.73 m2. PM2.5 exposure was associated with 1.3% (95% CI 0.6, 2.0) higher eGFR per 2.03 µg/m3 (interquartile range, IQR). PM2.5 exposure was also associated with elevated serum matrix metalloproteinase 2 (MMP-2) concentration, with 7.2% (95% CI 1.9, 12.8) higher MMP-2 per 2.03 µg/m3. There was a tendency towards an association between PM10 and higher levels of uric acid, but no associations were found with the other biomarkers. Associations with other air pollutants were null or inconsistent. CONCLUSION: In this large general population sample at low exposure levels, we found a surprising association between PM2.5 exposure and a higher renal filtration. It seems unlikely that particle function would improve renal function. However, increased filtration is an early sign of renal injury and may be related to the relatively healthy population at comparatively low exposure levels. Furthermore, PM2.5 exposure was associated with higher serum concentrations of MMP-2, an early indicator of renal and cardiovascular pathology.
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Contaminantes Atmosféricos , Biomarcadores , Exposición a Riesgos Ambientales , Tasa de Filtración Glomerular , Enfermedades Renales , Material Particulado , Humanos , Biomarcadores/sangre , Persona de Mediana Edad , Masculino , Femenino , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Suecia/epidemiología , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/epidemiología , Enfermedades Renales/sangre , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Anciano , Factor-23 de Crecimiento de Fibroblastos , Riñón/fisiopatología , Riñón/efectos de los fármacos , Óxidos de Nitrógeno/sangre , Óxidos de Nitrógeno/análisis , Óxidos de Nitrógeno/efectos adversos , AdultoRESUMEN
OBJECTIVE: Mercury is one of the heavy metal pollutants causing serious harm to human health. Quercetin was observed to repair kidney damage through the TLR4/TRIM32 pathway, and the detoxification effect of quercetin on heavy metal poisoning was observed. METHODS: For the study, the researchers divided 40 male mice from the KM strain into five groups: control, HgCl2, QU30, HgCl2+QU15, and HgCl2+QU30. The biological effects of those mice in each group were detected by the biochemical experiment, histopathology experiment and protein expression experiment respectively. RESULTS: HgCl2 had effects in increasing the level of malondialdehyde (MDA) and decreasing the activity of antioxidant enzymes (P < 0.05). HgCl2 induced inflammation by increasing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and Toll Like Receptor 4 (TLR-4) (P < 0.05). The expression of creatinine (CRE) and urea nitrogen (BUN) showed that HgCl2 promoted kidney injury. HgCl2 altered renal tissue integrity and TRIM32 expression which resulted in the increased autophagy associated protein levels of LC3. In contrast, quercetin reduced oxidative stress, autophagy, inflammation and histopathological changes (P < 0.05). CONCLUSION: Quercetin has the renal protection effects of anti-inflammation, anti-oxidation and anti-autophagy.
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Autofagia , Inflamación , Cloruro de Mercurio , Quercetina , Receptor Toll-Like 4 , Animales , Cloruro de Mercurio/toxicidad , Receptor Toll-Like 4/metabolismo , Quercetina/farmacología , Ratones , Masculino , Autofagia/efectos de los fármacos , Inflamación/inducido químicamente , Riñón/efectos de los fármacos , Riñón/patología , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Factores de Transcripción/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Antioxidantes/farmacologíaRESUMEN
Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.
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Ferroptosis , Factor 2 Relacionado con NF-E2 , Ubiquinona , Animales , Ferroptosis/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ubiquinona/metabolismo , Ratones , Ratas , Línea Celular , Masculino , Ratones Endogámicos C57BL , Riñón/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Doxorubicin (Dox) is widely used as a chemotherapy drug, while anethole (AN) is primarily known as the main aromatic component in various plant species. This research focused on the impact of AN on the cardiac and renal toxicity induced by Dox and to understand the underlying mechanisms. For cardiac toxicity, Wistar rats were categorized into four groups: a Control group; a Dox group, where rats received 2.5 mg/kg of Dox intraperitoneally every other day; and two Dox + AN groups, where animals were administered Dox (2.5 mg/kg/every other day, IP) along with 125 mg/kg or 250 mg/kg of AN, respectively. The renal toxicity study included similar groups, with the Dox group receiving a single dose of 20 mg/kg of Dox intraperitoneally on the tenth day, and the Dox + AN groups receiving 125 mg/kg and 250 mg/kg of AN for two weeks, alongside the same dose of Dox (20 mg/kg, IP, once on the 10th day). Parameters assessed included ECG, cardiac injury markers (CK, CK-MB, and LDH), and kidney function tests (Cr, BUN, uric acid, LDL, Kim-1, NGAL, and CysC). Antioxidant activity, lipid peroxidation, inflammation, and apoptotic markers were also monitored in heart and renal tissues. Gene expression levels of the TLR4/MyD88/NFκB pathway, along with Bax and Bcl-2, were evaluated. Dox significantly altered ECG, elevated cardiac injury markers, and renal function markers. It also augmented gene expressions of TLR4/MyD88/NFκB, amplified oxidative stress, inflammatory cytokines and apoptotic markers. Conversely, AN reduced cardiac injury markers and kidney function tests, improved ECG, diminished TLR4/MyD88/NFκB gene expression, and alleviated oxidative stress by increasing antioxidant enzyme activities and reducing inflammatory cytokines. AN also enhanced Bcl-2 levels and inhibited Bax and the cleavage of caspase-3 and 9. AN countered the lipid peroxidation, oxidative stress, inflammation, and apoptosis induced by Dox, marking it as a potential preventive strategy against Dox-induced nephrotoxic and cardiotoxic injuries.
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Derivados de Alilbenceno , Anisoles , Doxorrubicina , Riñón , Farmacología en Red , Ratas Wistar , Animales , Doxorrubicina/toxicidad , Ratas , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Anisoles/farmacología , Anisoles/toxicidad , Masculino , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Corazón/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Antibióticos Antineoplásicos/toxicidad , Antioxidantes/farmacología , FN-kappa B/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/prevención & control , Enfermedades Renales/metabolismoRESUMEN
The recent study delves into the role of both liraglutide and/or resveratrol on the nephropathic affection in rats treated with cyclosporine A (CsA). Rats were intoxicated with CsA (25 mg/kg) orally for 21 days and were supplemented with liraglutide (30 µg/kg) s/c daily and 20 mg/kg of resveratrol (20 mg/kg) orally. At the end of the experiment, serum samples and renal tissues were collected to determine renal damage markers, apoptotic markers, proinflammatory markers, and antioxidant status markers. Kidney function tests and antioxidant activity notably improved in the treated rats (CsA + Lir/CsA + Res/CsA + Lir + Res). Moreover, both Lir and/or Res enhanced Bcl-2 levels while down-regulating the Bax levels in rats treated with CsA. Interestingly, the immune-staining for tumor necrosis factor (TNF-α) was tested negative and mild positive in renal tissue of rats given Lir and/or Res while being treated with Cs A which indicated their anti-inflammatory effect that reduced the renal damage. The findings of this investigation revealed the ameliorative anti-inflammatory in addition to the antioxidant role of both liraglutide and resveratrol against the kidney damage caused due to CsA administration.
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Antioxidantes , Apoptosis , Ciclosporina , Riñón , Liraglutida , Resveratrol , Animales , Liraglutida/farmacología , Liraglutida/uso terapéutico , Resveratrol/farmacología , Resveratrol/uso terapéutico , Ciclosporina/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Masculino , Ratas , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Biomarcadores/metabolismo , Biomarcadores/sangre , Ratas Wistar , Enfermedades Renales/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismoRESUMEN
Phytic acid (PA) is a natural antioxidant with various biological activities, providing protective effects in multiple animals. Ochratoxin A (OTA) is a mold toxin commonly found in feed, which induces multi-organ damage, with kidney being the target organ of its toxicity. This study investigates the protective effects of PA on OTA-induced renal damage and its potential mechanisms in chicks. The results demonstrates that PA treatment restores OTA-induced renal pathological injuries, reverses the diminished activities of antioxidant enzymes, reduces the accumulation of malondialdehyde, and normalizes the expression of pro-inflammatory cytokines, which confirms that PA can alleviate OTA-induced renal damage. Further investigations reveal that OTA-induced renal injury accompanied by an increase in tissue iron content and the transcription levels of ferroptosis-related genes (TFR, ACSL4, and HO-1), and a decrease in the levels of SLC7A11 and GPX4. PA treatment reverses all these effects, indicating that PA mitigates OTA-induced renal ferroptosis. Moreover, PA supplementation improves intestinal morphology and mucosal function, corrects OTA-induced changes in the intestinal microbiota. Besides, PA microbiota transplantation alleviates renal inflammation and oxidative stress caused by OTA. In conclusion, PA plays a protective role against renal damage through the regulation of ferroptosis and the intestinal microbiota, possibly providing novel insights into the control and prevention of OTA-related nephrotoxicity.
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Pollos , Ferroptosis , Microbioma Gastrointestinal , Ocratoxinas , Ácido Fítico , Enfermedades de las Aves de Corral , Animales , Ocratoxinas/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Enfermedades de las Aves de Corral/inducido químicamente , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Ácido Fítico/administración & dosificación , Ácido Fítico/farmacología , Enfermedades Renales/veterinaria , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Alimentación Animal/análisis , Dieta/veterinaria , Masculino , Suplementos Dietéticos/análisisRESUMEN
BACKGROUND: Among patients undergoing percutaneous vascular intervention, contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality. Serum uric acid/albumin ratio (UAR) has emerged as a new marker associated with poor cardiovascular outcomes. We aimed to evaluate the relationship between UAR and CIN occurrence in patients treated for peripheral artery disease. METHODS: Patients underwent percutaneous intervention due to peripheral artery disease were enrolled. The primary endpoint was development of contrast related nephropathy. Patients were divided into 2 groups according to the CIN occurrence. RESULTS: A total of 663 patients were enrolled and mean age was 62 ± 10 years. After the intervention, 45 patients had CIN and 618 patients did not have CIN. Logistic regression analysis was performed to define the parameters of CIN. Male gender, diabetes, UAR, contrast volume, presence of coronary artery disease, and C-reactive protein levels were found significant in univariate analysis. However, only UAR was found significant in multivariate analysis (odds ratio 95% confidence interval: 3.426 (1.059-11.079), (P = 0.040)).Therefore, it is the only independent predictor for occurrence of CIN. CONCLUSIONS: UAR is a reliable scoring system, which predicts CIN in such patient group. This score is not only cost-effective also simple, which can be easily applied into the clinical practice.