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BACKGROUND: Cardiac dysfunction, including arrhythmias, may be one of the main clinical manifestations of Becker muscular dystrophy (BMD). Amiodarone is widely used to treat arrhythmia. However, multi-systemic toxicity caused by amiodarone, especially hepatotoxicity, should not be neglected. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, renal and coagulation in BDM patient with ABCB4 gene mutation. CASE PRESENTATION: We present a case of a 16-year-old boy admitted with heart failure and atrial fibrillation (AF). He was diagnosed with Becker muscular dystrophy (BMD) and gene testing showed comorbid mutations in gene DMD, ABCB4 and DSC2. Amiodarone was prescribed to control the paroxysmal atrial fibrillation intravenously. However, his liver enzyme levels were sharply elevated, along with cardiac shock, renal failure and coagulation disorders. After bedside continuous renal replacement therapy, the patient's liver function and clinical status rehabilitated. CONCLUSIONS: ABCB4 gene mutation might be involved in amiodarone-induced hepatotoxicity. Studies in a cohort might help to prove this hypothesis in the future.
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Subfamilia B de Transportador de Casetes de Unión a ATP , Amiodarona , Antiarrítmicos , Insuficiencia Cardíaca , Distrofia Muscular de Duchenne , Mutación , Humanos , Amiodarona/efectos adversos , Amiodarona/administración & dosificación , Masculino , Adolescente , Insuficiencia Cardíaca/inducido químicamente , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Antiarrítmicos/efectos adversos , Antiarrítmicos/uso terapéutico , Antiarrítmicos/administración & dosificación , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Fibrilación Atrial/tratamiento farmacológicoRESUMEN
INTRODUCTION: Imatinib is a first-line selective tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia. Although imatinib-induced hepatotoxicity may aggravate the patient's clinical condition and alter the treatment plan, the mechanism of imatinib-induced hepatotoxicity has rarely been investigated. CASE REPORT: We report a 51-year-old man, suffering from acute toxic hepatitis after 5 months of imatinib treatment for chronic myeloid leukemia. MANAGEMENT AND OUTCOME: The outcome was favorable after discontinuation of treatment with normalization of biological liver function after 12 weeks. The treatment was switched to nilotinib without any incidents. DISCUSSION: Regular liver function test monitoring is recommended during imatinib treatment. In fact of acute hepatic toxicity, treatment with imatinib should be stopped in the case of cytolysis more than five times the upper limit of normal.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Resultado del TratamientoRESUMEN
Valproic acid (VPA), a common anti-epileptic with prevalent use, has many side effects such as alopecia, abdominal discomfort, thrombocytopenia, etc. Other than those documented, publications cite the drug's rare side effects, such as hepatotoxicity, coagulation disorders, hyperammonemic encephalopathy, rhabdomyolysis, etc. We present the case of a 24-year-old man who was started on valproic acid after a seizure episode and developed mild transaminitis and rhabdomyolysis within 24 hours of drug initiation. Cessation of the drug led to the resolution of raised creatinine kinase and transaminase levels.
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This study aims to report a spontaneous and experimental intoxication in cattle by Melanthera latifolia (Asteraceae) for the first time, and to describe its epidemiological, clinical, and pathological findings. An outbreak of acute toxic hepatopathy in cattle occurred from December of 2021 to January of 2022 in a beef cattle farm from Rio Grande do Sul state, Southern Brazil, and resulted in 94 deaths from a herd of 430 animals. At necropsy, lesions consisted of enhanced lobular pattern of the liver, transmural gallbladder edema, and hemorrhages on the surface of multiple organs. The main microscopic lesion was marked hepatocellular necrosis in the centrilobular region associated with hemorrhage and infiltration of neutrophils. During the outbreak, multiple specimens of M. latifolia were noted in the paddocks where affected cattle were grazing and many showed signs of consumption. No other known acute hepatotoxic plants were found. Two 12-month-old steers were experimentally intoxicated with a single oral dose of the fresh plant (flowers, leaves, and less fibrous stalks). One bovine ingested a dose of 10 g/kg and was euthanized after 48 h, and the other ingested 15 g/kg and was euthanized 17 h later. Clinical signs, macroscopic, and microscopic lesions in both animals were similar to those observed in the spontaneous cases. Thus, this study demonstrates that M. latifolia was the cause of the outbreak of acute toxic hepatopathy with significant mortality in cattle. M. latifolia nor any plant of the genus Melantherahad ever been reported as toxic.
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Asteraceae , Enfermedades de los Bovinos , Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías , Intoxicación por Plantas , Bovinos , Animales , Intoxicación por Plantas/patología , Enfermedades de los Bovinos/epidemiología , Brasil/epidemiologíaRESUMEN
Background A liver injury could impair the integration of the body's organ system, which may cause complications that can lead to death. The dried red jujube fruit extract has the potential to protect the liver from toxic substances through its antioxidant properties. Aims To determine and analyze the hepatoprotective effect of dried red jujube fruit extract on aminotransferase levels against acetaminophen-induced acute hepatotoxicity. Methods Male Wistar rats were divided into five groups. The negative control group (G1) received carboxymethylcellulose sodium (CMC-Na) 1%. The positive control group (G2) received acetaminophen. The treatment group G3 received dried red jujube fruit extract 70 mg/kg BW + acetaminophen, G4 received dried red jujube fruit extract 140 mg/kg BW + acetaminophen, and G5 received dried red jujube fruit extract 280 mg/kg BW + acetaminophen. Dried red jujube fruit extract was given for 10 consecutive days. Acetaminophen (3 g/kg BW) was given on the ninth day. Blood samples were collected, and aminotransferase levels were measured on the 11th day. Results Kruskal-Wallis comparison test showed significant differences (p < 0.01) between all groups on alanine aminotransferase (ALT; p = 0.003) and aspartate aminotransferase (AST; p = 0.001) levels. Mann-Whitney post hoc test showed significant differences (p < 0.01) between G2:G3, G2:G4, and G2:G5 groups on ALT and AST levels. Pearson correlation test showed a significant negative correlation (p < 0.01; r = -1) between all given doses of dried red jujube fruit extract on ALT (p = 0.000; r = -0.778) and AST (p = 0.000; r = -0.774) levels. Conclusion The dried red jujube fruit extract has a hepatoprotective effect on aminotransferase levels against acetaminophen-induced acute hepatotoxicity at 70 mg/kg BW, 140 mg/kg BW, and 280 mg/kg BW (the most effective dose), and there was a negative correlation between all doses and the aminotransferase levels.
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The toxicity of acetaminophen (N-acetyl-para-aminophenol (APAP)) is the most frequent cause of drug-induced liver damage. Galium aparine L. (GA) is traditionally used to treat jaundice. We aimed to investigate the hepatoprotective potential of GA in the APAP-induced hepatic encephalopathy (HE) rat model. Qualitative phytochemical characterization of GA was performed by LC/Q-TOF/MS analysis. Wistar rats were pretreated with GA (250 and 500 mg/kg b.wt. per oral) for five days. On the 6th day, the rats were exposed to APAP (1500 mg/kg b.wt. oral gavage) and behavioral tests (open field and passive avoidance tests) were applied on the 7th and 8th days. The animals were killed, and biochemical and histopathological parameters were assessed in blood and hepatic specimens. GA pretreated rats exhibited a significant reduction in APAP-induced liver damage, evidenced by the reduction in liver necrosis and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (BIL). GA demonstrated an anxiolytic effect, as seen in the acquisition trial and grooming behavior. The short-term memory performances of animals were not changed in all groups, suggesting that APAP intoxication did not affect hippocampal function. These results show that GA extract markedly exerts hepatoprotective activity, while its effect on hepatic encephalopathy was limited.
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Ansiolíticos , Enfermedad Hepática Inducida por Sustancias y Drogas , Galium , Encefalopatía Hepática , Acetaminofén/toxicidad , Alanina Transaminasa , Animales , Ansiolíticos/farmacología , Aspartato Aminotransferasas , Bilirrubina , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Encefalopatía Hepática/patología , Hígado , Extractos Vegetales/farmacología , Ratas , Ratas WistarRESUMEN
Silver nanoparticles (Ag NPs or nanosilver) have pulled in expanding interest because of their novel physical, substance, and organic properties contrasted with their full scale scaled partners. The goal of this study was to investigate if Avena sativa (AVS) extract could ameliorate Ag NPs toxicity-induced alterations in liver structure and function, DNA damage, apoptosis, and oxidative stress. Twenty adult male rats were assigned randomly to four groups: control, AVS (intragastrically, 5 g/Kg body weight/day) for 2 weeks, Ag NPs (400 mg/kg body weight/day) for 1 week as acute toxicity and Ag NPs + AVS (same therapy of Ag NPs as acute toxicity with AVS). This study demonstrated a statistical significant increase in serum levels of liver function tests (AST, ALT, ALP and globulin), liver DNA damage, apoptotic P53 and Malondialdehyde after Ag NPs administration when compared to control group. Conversely, statistical significant decreases were detected in serum albumin, total proteins, liver reduced glutathione, catalase, superoxide dismutase, glutathione S-transferase and anti-apoptotic Bcl2 in Ag NPs group as compared to control group. Interestingly, treatment of Ag NPs with AVS (Ag Nps + AVS) was associated with significant improvements of the studied parameters, liver structure and functions. Avena sativa (AVS) extract could scavenge free radicals producing beneficial effects against acute Ag NPs hepatotoxicity in rats induced through activation of oxidative stress and apoptosis.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Nanopartículas del Metal , Animales , Apoptosis , Avena , Peso Corporal , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Daño del ADN , Hígado , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Estrés Oxidativo , Ratas , Plata/química , Plata/toxicidadRESUMEN
Drug overdose has been a public health burden in the United States. Repeated use of cocaine and heroin may increase the risk of severe acute liver failure. We present the case of a middle-aged man with no significant past medical condition except a chronic history of drug abuse who presented to our hospital after an overdose of cocaine and heroin. Patient received Narcan by paramedics and continued treatment in the emergency room (ER). Patient has exhibited multiple organ failures, such as acute liver failure, rhabdomyolysis, acute kidney injury, and acute respiratory hypoxic hypercapnic respiratory failure likely due to respiratory center depression. The patient was placed on a non-rebreather mask then a bilevel positive airway pressure (BiPAP) machine. Patient failed the BiPAP trial, was intubated and later extubated after five days, and discharged on room air. The patient was admitted to the intensive care unit due to toxic encephalopathy. Liver enzymes were markedly elevated during admission and trended down after supportive management, Narcan, and N-acetylcysteine treatment.
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Selective androgen receptor modulators (SARMs) have been developed as an alternate to traditional anabolic steroids due to their favorable effects on the bones and muscles without androgenic side effects. They are very popular among athletes and bodybuilders and are available online or over the counter. The FDA has warned of their side effects including liver injury. Here we present the case of a 29-year-old patient who presented with jaundice, fatigue, and elevated liver function tests after starting SARM supplements. His symptoms improved and eventually resolved with stopping the supplements. The purpose of this case report is to raise awareness and educate clinicians of the potential side effect of hepatotoxicity of these supplements that can help in its early identification and management.
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ABSTRACT: In this study, an outbreak of spontaneous poisoning by Dodonaea viscosa (D. viscosa) in a herd of dairy cattle in the municipality of Capão do Leão, Rio Grande do Sul, was investigated. Three deaths occurred in a batch of 16 Jersey cattle, aged between three and four years, kept in a native field. The clinical signs observed were apathy, decreased production, and anorexia, with death occurring within approximately 48 h after the onset of signs. The three cattle were necropsied, and tissue samples were sent for histopathological examination. Necropsy findings included serosanguineous fluid in the abdominal cavity, intestines with congested serosa, and marked mesenteric edema. The mucosa of the abomasum of two of the animals was hemorrhagic with bloody content, and among the ruminal content of a bovine, leaves with morphological characteristics compatible with D. viscosa were observed. The livers of the three animals were enlarged, with accentuation of the lobular pattern. Histologically, centrilobular coagulation necrosis with congestion and hemorrhage was observed in the liver. Vacuolization and degeneration of hepatocytes were observed in the mid-zonal and periportal regions. The diagnosis of poisoning by D. viscosa leaves was based on epidemiological data, necropsy findings, and histopathological alterations. The presence of the plant in the rumen and in the grazing site of the affected cattle was essential for the diagnosis.
RESUMO: Neste trabalho, é descrito um surto de intoxicação espontânea por Dodonaea viscosa (D. viscosa) ocorrido em um rebanho de bovinos leiteiros, no município de Capão do Leão, no Rio Grande do Sul. Ocorreram três mortes em um lote de 16 bovinos da raça Jersey com idades entre três e quatro anos, mantidos em campo nativo. Os sinais clínicos observados foram apatia, queda na produção e anorexia, com morte em aproximadamente 48 horas após o início dos sinais. Os três bovinos foram necropsiados, e amostras de tecidos foram encaminhadas para exame histopatológico. Os achados de necropsia incluíam líquido serossanguinolento na cavidade abdominal, intestinos com serosas congestas e marcado edema de mesentério. A mucosa do abomaso de dois animais apresentava-se hemorrágica com conteúdo sanguinolento e, em meio ao conteúdo ruminal de um bovino foram observadas folhas com caracteres morfológicos compatíveis com D. viscosa. O fígado dos três animais estava aumentado, com acentuação do padrão lobular. Histologicamente no fígado havia necrose de coagulação centrolobular com congestão e hemorragia. Nas regiões médio-zonal e periportal observou-se vacuolização e degeneração dos hepatócitos. O diagnóstico de intoxicação pelas folhas D. viscosa foi baseado nos dados epidemiológicos, nos achados de necropsia e nas alterações histopatológicas. A presença da planta no rúmen e no local de pastoreio dos bovinos afetados foi fundamental para o diagnóstico.
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In this study, an outbreak of spontaneous poisoning by Dodonaea viscosa (D. viscosa) in a herd of dairy cattle in the municipality of Capão do Leão, Rio Grande do Sul, was investigated. Three deaths occurred in a batch of 16 Jersey cattle, aged between three and four years, kept in a native field. The clinical signs observed were apathy, decreased production, and anorexia, with death occurring within approximately 48 h after the onset of signs. The three cattle were necropsied, and tissue samples were sent for histopathological examination. Necropsy findings included serosanguineous fluid in the abdominal cavity, intestines with congested serosa, and marked mesenteric edema. The mucosa of the abomasum of two of the animals was hemorrhagic with bloody content, and among the ruminal content of a bovine, leaves with morphological characteristics compatible with D. viscosa were observed. The livers of the three animals were enlarged, with accentuation of the lobular pattern. Histologically, centrilobular coagulation necrosis with congestion and hemorrhage was observed in the liver. Vacuolization and degeneration of hepatocytes were observed in the mid-zonal and periportal regions. The diagnosis of poisoning by D. viscosa leaves was based on epidemiological data, necropsy findings, and histopathological alterations. The presence of the plant in the rumen and in the grazing site of the affected cattle was essential for the diagnosis.(AU)
Neste trabalho, é descrito um surto de intoxicação espontânea por Dodonaea viscosa (D. viscosa) ocorrido em um rebanho de bovinos leiteiros, no município de Capão do Leão, no Rio Grande do Sul. Ocorreram três mortes em um lote de 16 bovinos da raça Jersey com idades entre três e quatro anos, mantidos em campo nativo. Os sinais clínicos observados foram apatia, queda na produção e anorexia, com morte em aproximadamente 48 horas após o início dos sinais. Os três bovinos foram necropsiados, e amostras de tecidos foram encaminhadas para exame histopatológico. Os achados de necropsia incluíam líquido serossanguinolento na cavidade abdominal, intestinos com serosas congestas e marcado edema de mesentério. A mucosa do abomaso de dois animais apresentava-se hemorrágica com conteúdo sanguinolento e, em meio ao conteúdo ruminal de um bovino foram observadas folhas com caracteres morfológicos compatíveis com D. viscosa. O fígado dos três animais estava aumentado, com acentuação do padrão lobular. Histologicamente no fígado havia necrose de coagulação centrolobular com congestão e hemorragia. Nas regiões médio-zonal e periportal observou-se vacuolização e degeneração dos hepatócitos. O diagnóstico de intoxicação pelas folhas D. viscosa foi baseado nos dados epidemiológicos, nos achados de necropsia e nas alterações histopatológicas. A presença da planta no rúmen e no local de pastoreio dos bovinos afetados foi fundamental para o diagnóstico.(AU)
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Animales , Bovinos , Intoxicación , Coagulación Sanguínea , Hepatocitos , Sapindaceae , Fluconazol , NecrosisRESUMEN
Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug, but it comes with a high risk of drug-induced liver injury (DILI). Despite the quinone-imine adduct pathways, the immunotoxicity is recently considered as another factor for DILI. However, such immune responses are still elusive. In the present study, investigation of the immune response in the acute hepatotoxicity model of TgCYP3A4/hPXR-humanized mice was conducted by administration of DCF and DCF metabolites, respectively. In a single dose intraperitoneal injection of 80 mg/kg DCF, the pharmacokinetic results showed the major DCF metabolites, including 4'-hydroxy-diclofenac (4'-OH-DCF), 5-hydroxy-diclofenac (5-OH-DCF) and diclofenac glucuronide (DCF-G) were generated after DCF treatment. Not only DCF, but those DCF metabolites could also directly cause different degrees of acute liver injury as significantly increased the serum ALT levels in a short time period in the TgCYP3A4/hPXR-humanized mice. Furthermore, the three DCF metabolites could directly stimulate the significant elevation of serum immune-related factors in varying degrees. Transcriptome analysis revealed the differentially expressed genes in the liver of DCF-G treated mice were mostly involved with the "immune system process" and "cell death" and related to "IL-17 signaling pathway" and "TNF-α signaling pathway", but 5-OH-DCF had little effect on the expressions of those genes. These results indicate that the metabolite DCF-G plays an important role in the activation of the hepatic immune system, which might be involved in the pathogenesis of DCF-induced acute liver injury.
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Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Diclofenaco/efectos adversos , Diclofenaco/farmacocinética , Hígado/inmunología , Hígado/metabolismo , Alanina Transaminasa/sangre , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacocinética , Muerte Celular/efectos de los fármacos , Citocinas/sangre , Diclofenaco/administración & dosificación , Diclofenaco/análogos & derivados , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Glucurónidos/administración & dosificación , Glucurónidos/efectos adversos , Glucurónidos/farmacocinética , Humanos , Inmunidad/efectos de los fármacos , Inyecciones Intraperitoneales , Interleucina-17/genética , Hígado/lesiones , Hígado/patología , Ratones Transgénicos , Mapas de Interacción de Proteínas , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacosRESUMEN
Acetaminophen (APAP) is one of the most used analgesics and antipyretic agents in the world. Intoxication with APAP is the main cause of acute liver toxicity in both the US and Europe. Spore-forming probiotic bacteria have the ability to resist harsh gastric and intestinal conditions. The aim of this study was to investigate the possible protective effect of Bacillus (B) species (sp) spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, B. coagulans) against hepatotoxicity induced by APAP in rats. A total of 35 rats were randomly divided into seven groups: group I served as control; group II received silymarin; group III received MegaSporeBioticTM (MSB); group IV received APAP and served as the model of hepatotoxicity; group V received APAP and silymarin; group VI received APAP and MSB; group VII received APAP, silymarin and MSB. The livers for histopathological examination and blood samples were collected on the last day of the experiment. We determined aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (TAC) levels and zonula occludens (ZO-1), tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) expression. APAP overdose increased AST and ALT. It slowly decreased TAC compared to the control group, but pretreatment with silymarin and MSB increased TAC levels. Elevated plasma concentrations were identified for ZO-1 in groups treated with APAP overdose compared with those without APAP or receiving APAP in combination with silymarin, MSB or both. The changes were positively correlated with the levels of other proinflammatory cytokines (TNF-α, IL-1ß). In addition, histopathological hepatic injury was improved by preadministration of MSB or silymarin versus the disease model group. Bacillus sp spores had a protective effect on acute hepatic injury induced by APAP. Pretreatment with MSB resulted in a significant reduction in serum AST, ALT, TNF-α, IL-1ß, ZO-1, TAC and also hepatocyte necrosis, similar to the well-known hepatoprotective agent-silymarin.
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Acetaminofén/efectos adversos , Bacillus , Fallo Hepático Agudo/prevención & control , Hígado/metabolismo , Probióticos/farmacología , Esporas Bacterianas , Acetaminofén/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Interleucina-1beta/sangre , Hígado/patología , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/patología , Masculino , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangre , Proteína de la Zonula Occludens-1/sangreRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The liver and kidney are among the most important organs in the body, where metabolic and elimination functions take place. During this process, liver and kidneys may suffer damage due to ingestion or formation of toxic metabolites leading to organ loss and even death. Artichoke (Cynara scolymus L.) leaf has long been recognized as a popular herbal remedy in traditional medicines with beneficial effects on liver. AIM OF THE STUDY: In phytotherapy leaves are the part used to support the liver functions and for treatment of damage induced by various toxins, while fleshy receptacle is cooked as meal to support liver homeostasis. However, effects of other plant parts on liver such as stems, bracts have not much attracted the attention of scientific community so far. In this study we investigated comparatively the hepatoprotective and nephroprotective effects of different plant parts of artichoke, i.e. receptacles, outer bracts, inner bracts, and stems with that of leaves upon paracetamol-induction in rats. MATERIALS AND METHODS: Aqueous ethanol (80%) extracts obtained from the different parts of artichoke were administered for five consecutive days after paracetamol induction to rats. At the end of experimental period blood samples from the experimental animals were taken for biochemical tests, while livers and kidneys were removed for further histopathological evaluation. RESULTS: The histopathological examinations of liver and kidney tissues revealed that the receptacle and stem extracts of the artichoke were the most effective parts by improving the experimentally induced pathology in both liver and kidney. Biochemical tests also supported the histopathological data; receptacle, stem and bract extracts reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, but not alkaline phosphatase (ALP), creatinine and blood urea nitrogen (BUN) levels. CONCLUSIONS: Histopathological and biochemical studies have shown that receptacle and stem extracts of artichoke were found to exert higher protective activity on liver and kidney damage induced by paracetamol comparing to its bract and leaf extracts, the latest is officially recognized as herbal remedy.
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Lesión Renal Aguda/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cynara scolymus/química , Fitoterapia/métodos , Extractos Vegetales/farmacología , Acetaminofén/toxicidad , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Etanol/química , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Tallos de la Planta/química , RatasRESUMEN
In the past few decades, upconversion nanoparticles (abbreviated as UCNPs) have been more widely applied in the biomedical fields, such as in vitro and in vivo upconversion fluorescent bioimaging, photodynamic therapy, biological macromolecular detection, imaging mediated drug delivery and so on. But meanwhile, there is still not much research on the acute toxicity of upconversion nanoparticles in vivo, such as acute hepatotoxicity. In this work, we studied the in vivo biodistribution and acute hepatotoxicity of multimodal targeted contrast agent NaLuF4:Gd,Yb,Er-PEG/PEI-FA nanoprobe, which were synthesized by the solvothermal method and modified with Polyethylene glycol (PEG), Polyetherimide (PEI), folic acid (FA) on the surface. The acute hepatotoxicity in mice was systematically assessed after tail vein injection of different concentration of UCNPs. The results showed that NaLuF4:Gd,Yb,Er-PEG/PEI-FA nanoparticles with an average diameter of 44.5 ± 10.4 nm, and three typical upconversion fluorescence emission bands at 520 nm, 540 nm and 660 nm under the excitation of 980 nm laser. In vivo distribution experiments results demonstrated that approximately 87% of UCNPs injected through the tail vein accumulate in the liver. In the acute hepatotoxicity test, the intravenously injection dose of UCNPs was 10, 40, 70 and 100 mg/kg, respectively. The body weight, blood routine, serum biochemistry, histomorphology and liver oxidative stress were detected and observed no significant acute hepatotoxicity damage under the injection dose of 100 mg/kg. In conclusion, NaLuF4:Gd,Yb,Er-PEG/PEI-FA nanoprobes are safe and reliable, and have potential applications in the field of tumor targeted multimodal imaging.
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Medios de Contraste/toxicidad , Colorantes Fluorescentes/toxicidad , Gadolinio/toxicidad , Hígado/efectos de los fármacos , Hígado/diagnóstico por imagen , Imagen Multimodal/métodos , Nanopartículas/efectos adversos , Animales , Medios de Contraste/administración & dosificación , Medios de Contraste/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Colorantes Fluorescentes/administración & dosificación , Colorantes Fluorescentes/metabolismo , Gadolinio/administración & dosificación , Gadolinio/metabolismo , Inyecciones Intravenosas , Ratones Endogámicos ICR , Nanopartículas/administración & dosificación , Nanopartículas/metabolismo , Tamaño de la Partícula , Seguridad , Distribución TisularRESUMEN
Acetaminophen (APAP)-induced acute hepatotoxicity is the leading cause of drug-induced acute liver failure. The aim of this study was to evaluate the effects of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) on the protection of APAP-induced hepatotoxicity in mice. Mice were pretreated with a single dose of tempol (20 mg/kg per day) orally for 7 days. On the seventh day, mice were injected with a single dose of APAP (300 mg/kg) to induce acute hepatotoxicity. Our results showed that tempol treatment markedly improved liver functions with alleviations of histopathological damage induced by APAP. Tempol treatment upregulated levels of antioxidant proteins, including superoxide dismutase, catalase, and glutathione. Also, phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) and protein expression of nuclear factor erythroid 2-related factor (Nrf 2) and heme oxygense-1 (HO-1) were all increased by tempol, which indicated tempol protected against APAP-induced hepatotoxicity via the PI3K/Akt/Nrf2 pathway. Moreover, tempol treatment decreased pro-apoptotic protein expressions (cleaved caspase-3 and Bax) and increased anti-apoptotic Bcl-2 in liver, as well as reducing apoptotic cells of TUNEL staining, which suggested apoptotic effects of tempol treatment. Overall, we found that tempol normalizes liver function in APAP-induced acute hepatotoxicity mice via activating PI3K/Akt/Nrf2 pathway, thus enhancing antioxidant response and inhibiting hepatic apoptosis.
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This study based on~1H-NMR urine metabolomics technique combined with biochemical indicators to focus on studying the acute hepatotoxicity mechanism of Artemisia argyi essential oil( AAEO). In order to further explore the acute hepatotoxicity mechanism of AAEO,the researchers collected the urine nuclear magnetic data of rats in different periods of high and low doses of olive oil and AAEO group. Using the principal component analysis( PCA) and orthogonal partial least squares-discrimination analysis( OPLSDA) to analyze the endogenous small molecule metabolites in rat urine to study the effects of AAEO on the metabolic process of normal rats. The results showed there was a significant difference between the olive oil group and the AAEO group,the PCA scores chart demonstrated that there was no obvious separation tendency in the urine of olive oil group rats 0-6,6-12,12-24 h,and the metabolic components were distributed in aggregation pattern. The urinary metabolic trajectory of the rats in the AAEO group was conspicuously separated at 0-6,6-12,12-24 h. The experiments proved that the analysis of metabolites by~1H-NMR found that AAEO caused metabolic disorders in rats and produced acute hepatotoxicity. After metabolite differential comparison,it was speculated that the mechanism of acute hepatotoxicity may be involved in the tricarboxylic acid cycle and energy metabolism,while the citrate and oleanolic acid would be the potential biomarkers. This study discussed that the acute hepatotoxicity mechanism of AAEO was used to provide the experimental data for the clinical prescription of Artemisia argyi.
Asunto(s)
Artemisia , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Metabolómica , Aceites Volátiles , Espectroscopía de Protones por Resonancia Magnética , RatasRESUMEN
Microcystins produced by some cyanobacteria can cause damages to the liver and kidneys of aquatic animals. In the natural water with cyanobacterial blooms, silver carp may suffer from the most serious affect of the bloom due to their filtering these cyanobacteria and ingesting them as food. In the present study, silver carp was exposed to microcystin-LR by using the method of intraperitoneal injection first to determine the acute toxicity of microcystin-LR on silver carp and then to determine the activity of inflammatory protein and content of inflammatory factors from the serum of silver carp following a subacute exposure of microcystin-LR at doses of 104.9⯵gâ¯kg-1 (1/5 of LD50) or 262.1⯵gâ¯kg-1 (1/2 of LD50). The results showed that MC-LR exposure increased fish liver index and promoted the activities of fish serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating the hepatotoxicity of MC-LR on the fish. Moreover, MC-LR exposure also increased the number of leukocytes, complement C3 level, lysozyme activity (at the first 9â¯h of exposure), and the contents of cytokines TNF-α, IL-1ß and IFN-γ in fish serum. In addition, a significant increase in IgM level was observed in the serum and head kidney of silver carp following MC-LR exposure. This result suggests that semi-lethal doses of MC-LR exposure is not only hepatotoxic but also immunotoxic to silver carp.
Asunto(s)
Carpas , Hígado/efectos de los fármacos , Microcistinas/toxicidad , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Carpas/inmunología , Carpas/metabolismo , Citocinas/sangre , Riñón Cefálico/inmunología , Inmunoglobulina M/sangre , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Recuento de Leucocitos , Hígado/metabolismo , Toxinas MarinasRESUMEN
This study based on~1H-NMR urine metabolomics technique combined with biochemical indicators to focus on studying the acute hepatotoxicity mechanism of Artemisia argyi essential oil( AAEO). In order to further explore the acute hepatotoxicity mechanism of AAEO,the researchers collected the urine nuclear magnetic data of rats in different periods of high and low doses of olive oil and AAEO group. Using the principal component analysis( PCA) and orthogonal partial least squares-discrimination analysis( OPLSDA) to analyze the endogenous small molecule metabolites in rat urine to study the effects of AAEO on the metabolic process of normal rats. The results showed there was a significant difference between the olive oil group and the AAEO group,the PCA scores chart demonstrated that there was no obvious separation tendency in the urine of olive oil group rats 0-6,6-12,12-24 h,and the metabolic components were distributed in aggregation pattern. The urinary metabolic trajectory of the rats in the AAEO group was conspicuously separated at 0-6,6-12,12-24 h. The experiments proved that the analysis of metabolites by~1H-NMR found that AAEO caused metabolic disorders in rats and produced acute hepatotoxicity. After metabolite differential comparison,it was speculated that the mechanism of acute hepatotoxicity may be involved in the tricarboxylic acid cycle and energy metabolism,while the citrate and oleanolic acid would be the potential biomarkers. This study discussed that the acute hepatotoxicity mechanism of AAEO was used to provide the experimental data for the clinical prescription of Artemisia argyi.
Asunto(s)
Animales , Ratas , Artemisia , Enfermedad Hepática Inducida por Sustancias y Drogas , Metabolómica , Aceites Volátiles , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
A toxicoproteomic study was performed on liver of rats treated with retrorsine (RTS), a representative hepatotoxic pyrrolizidine alkaloid at a toxic dose (140 mg/kg) known to cause severe acute hepatotoxicity. By comparing current data with our previous findings in mild liver lesions of rats treated with a lower dose of RTS, seven proteins and three toxicity pathways of vascular endothelial cell death, which was further verified by observed sinusoidal endothelial cell losses, were found uniquely associated with retrorsine-induced hepatotoxicity. This toxicoproteomic study of acute pyrrolizidine alkaloid intoxication lays a foundation for future investigation to delineate molecular mechanisms of pyrrolizidine alkaloid-induced hepatotoxicity.