Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PT...Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.展开更多
Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then...Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture.Moreover,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured.Results:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde levels.Immunohistochemical results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract.Moreover,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and COX-2.Conclusions:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.展开更多
We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic ...We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.展开更多
Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing S...Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.展开更多
The prevalence of alcoholic liver disease and non-alcoholic liver disease patients has nearly doubled over the past decades worldwide. Alcoholic liver disease among patients with chronic liver disease has increased wi...The prevalence of alcoholic liver disease and non-alcoholic liver disease patients has nearly doubled over the past decades worldwide. Alcoholic liver disease among patients with chronic liver disease has increased with arisen due to alcohol consumption and obesity. The diagnosis plays a crucial role in treating such conditions based on the stages of liver functioning. The elevated liver enzymes are the key characterizing of identifying the alcoholic liver disease (ALD) and NAFLD. Later on, there is a progression of the disease conditions by developing fibrosis and cirrhosis, leading to liver carcinoma. The other state, steatohepatitis, is associated with an increase in liver-related and can lead to mortality. Risk factors for both diseases are growing, leading to various complications in health. There is no specific treatment up to date for these conditions, but statins play a crucial role in managing several liver disease conditions. The commonly used drug is hydroxymethylglutaryl coenzyme A (HMG Co-A) reductase inhibitors. It is also known as statins, which help normalize liver enzymes in patients with elevated plasma aminotransferases. As a result, external liver damage is considered safe for the liver as the Statin medication at low to moderate dose usage. OBJECTIVES: The main scope of this review is to study the various factors like pharmacological actions, adverse events, and biochemical and liver cell imaging results in patients with ALD and NAFLD. The different types of statins used in alcoholic and non-alcoholic patients’ clinical data for the safety of the statin therapy were concluded in this review. Fatty liver changes of both liver disease conditions were studied using different drugs. The other liver enzymes like Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl Transferase (GGT), and the effectiveness of Statin therapy are considered vital concepts in this review.展开更多
Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compound...Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compounds based on network pharmacology.Methods:Using network pharmacology,a"traditional Chinese medicine-chemical composition-key target-pathway"analysis was conducted on Radix Paeoniae Alba for the treatment of Toosendan Fructus-induced hepatotoxicity.The possible mechanism of action was analyzed in terms of function.Results:The core targets,such as interleukin(IL)-6,tumor necrosis factor(TNF),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),Jun proto-oncogene(JUN),caspase-3,estrogen receptor 1(ESR1),and aryl hydrocarbon receptor(AHR)were screened from the targets of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity.Biological process(BP)of toxic targets(BP terms)involved"response to drug;activation of cysteine-type endopeptidase activity involved in apoptotic process,”positive regulation of transcription.Cellular components(CC terms)mainly involved cytosol and membrane rafts.Molecular function(MF)terms included"protein homodimerization activity,"RNA polymerase II transcription factor activity and enzyme binding,etc."The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway included the TNF signaling pathway,cancer pathways,and apoptosis.Conclusion:Radix Paeoniae Alba might alleviate Toosendan Fructus-induced hepatotoxicity through IL6,TNF,HSP90AA1,PPARG,PTGS2,HMOX1,and other targets,possibly via the activation of cysteine-type endopeptidase activity involved in these pathways.展开更多
The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters...The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.展开更多
BACKGROUND Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage.We present the case of a massive ruptured hepatic adenoma with p...BACKGROUND Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage.We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation.This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma.CASE SUMMARY A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day.She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma.She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure,hepatic failure,and hemodynamic instability,known as toxic liver syndrome.In the setting of uncontrolled hemorrhage and toxic liver syndrome,a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later.She tolerated the anhepatic stage well,and has done well over one year later.CONCLUSION When toxic liver syndrome is recognized,liver transplantation with or withouthepatectomy should be considered before the patient becomes unstable.展开更多
The incidence of inflammatory bowel diseases(IBD)is rising worldwide.The therapeutic options for IBD are expanding,and the number of drugs with new targets will rapidly increase in coming years.A rapid step-up approac...The incidence of inflammatory bowel diseases(IBD)is rising worldwide.The therapeutic options for IBD are expanding,and the number of drugs with new targets will rapidly increase in coming years.A rapid step-up approach with close monitoring of intestinal inflammation is extensively used.The fear of side effects represents one the most limiting factor of their use.Despite a widespread use for years,drug induced liver injury(DILI)management remains a challenging situation with Azathioprine and Methotrexate.DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies.The aim of this review is to report incidence,physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.展开更多
Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can re...Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can reach up to 50%in different studies.Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD,while primary sclerosing cholangitis is the most specific.Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists.The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD,associated diseases or to the therapies used.展开更多
Microplastics(MPs)have become a significant concern for their potential toxicity.However,the correlation between the size of plastic particles and their toxicity remains inconclusive.Here,we investigate the toxic effe...Microplastics(MPs)have become a significant concern for their potential toxicity.However,the correlation between the size of plastic particles and their toxicity remains inconclusive.Here,we investigate the toxic effects of different sizes(80 nm,800 nm,8μm and 80μm)polystyrene MPs(PS-MPs)on the model organism Nile tilapia(Oreochromis niloticus).The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body.H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group.Ed U labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group.The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group.The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group.In conclusion,this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity.All the above lay the foundation for further study on the pathological damage of MPs to other organisms.展开更多
The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely di...The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely distributed in eutrophic waters.MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals.However,the underlying mechanisms of MCLR-induced liver toxicity are unclear.Herein,we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice.We established the first single-cell atlas ofmouse livers in response to MC-LR.Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treatedwith MC-LR are highly heterogeneous.Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3,which potentially contributed to hepatocyte apoptosis in response to MC-LR.Moreover,MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes.Furthermore,the MC-LR increased several subtypes of CD8+T cells with highly expressed multiple cytokines and chemokines.Overall,apart from directly inducing hepatocytes apoptosis,MC-LR activated proinflammatory Kupffer cell and CD8+T cells,and their interaction may constitute a hostile microenvironment that contributes to liver injury.Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.展开更多
Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we...Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.展开更多
The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low succe...The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low success rates and high attrition of drug candidates1. The current methodology of new drug R&D is deeply influenced by the idea of allopathic medicine, which directly inhibits biological targets.展开更多
Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer,supported by favorable outcomes and good tolerance.However,it is linke...Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer,supported by favorable outcomes and good tolerance.However,it is linked to multiple immune manifestations,referred to as immune-related adverse events(irAEs).These adverse events frequently affect the skin,colon,endocrine glands,lungs,and liver.The gastrointestinal system is one of the most commonly affected organ systems and is responsible for the most frequent emergency visits resulting from irAEs.However,because immune checkpoint inhibitors are a recent addition to our arsenal of cancer drugs,many health-care providers remain unfamiliar with the management of irAEs.Gastroenterologists involved in the treatment of oncology patients who have received checkpoint inhibitors are currently encountering cases of abdominal pain,diarrhea,and other nonspecific symptoms that may be challenging to manage.This article reviews the gastrointestinal,hepatic,and pancreatic toxicities of checkpoint inhibitors and provides an approach to their diagnosis and recommended workup.It also highlights the management of irAEs according to their toxicity grading and specifically discusses the instances in which corticosteroids should be administered and/or the immune checkpoint inhibitors should be withheld.展开更多
文摘Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.
文摘Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture.Moreover,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured.Results:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde levels.Immunohistochemical results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract.Moreover,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and COX-2.Conclusions:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.
文摘We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.
文摘Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.
文摘The prevalence of alcoholic liver disease and non-alcoholic liver disease patients has nearly doubled over the past decades worldwide. Alcoholic liver disease among patients with chronic liver disease has increased with arisen due to alcohol consumption and obesity. The diagnosis plays a crucial role in treating such conditions based on the stages of liver functioning. The elevated liver enzymes are the key characterizing of identifying the alcoholic liver disease (ALD) and NAFLD. Later on, there is a progression of the disease conditions by developing fibrosis and cirrhosis, leading to liver carcinoma. The other state, steatohepatitis, is associated with an increase in liver-related and can lead to mortality. Risk factors for both diseases are growing, leading to various complications in health. There is no specific treatment up to date for these conditions, but statins play a crucial role in managing several liver disease conditions. The commonly used drug is hydroxymethylglutaryl coenzyme A (HMG Co-A) reductase inhibitors. It is also known as statins, which help normalize liver enzymes in patients with elevated plasma aminotransferases. As a result, external liver damage is considered safe for the liver as the Statin medication at low to moderate dose usage. OBJECTIVES: The main scope of this review is to study the various factors like pharmacological actions, adverse events, and biochemical and liver cell imaging results in patients with ALD and NAFLD. The different types of statins used in alcoholic and non-alcoholic patients’ clinical data for the safety of the statin therapy were concluded in this review. Fatty liver changes of both liver disease conditions were studied using different drugs. The other liver enzymes like Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl Transferase (GGT), and the effectiveness of Statin therapy are considered vital concepts in this review.
文摘Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compounds based on network pharmacology.Methods:Using network pharmacology,a"traditional Chinese medicine-chemical composition-key target-pathway"analysis was conducted on Radix Paeoniae Alba for the treatment of Toosendan Fructus-induced hepatotoxicity.The possible mechanism of action was analyzed in terms of function.Results:The core targets,such as interleukin(IL)-6,tumor necrosis factor(TNF),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),Jun proto-oncogene(JUN),caspase-3,estrogen receptor 1(ESR1),and aryl hydrocarbon receptor(AHR)were screened from the targets of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity.Biological process(BP)of toxic targets(BP terms)involved"response to drug;activation of cysteine-type endopeptidase activity involved in apoptotic process,”positive regulation of transcription.Cellular components(CC terms)mainly involved cytosol and membrane rafts.Molecular function(MF)terms included"protein homodimerization activity,"RNA polymerase II transcription factor activity and enzyme binding,etc."The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway included the TNF signaling pathway,cancer pathways,and apoptosis.Conclusion:Radix Paeoniae Alba might alleviate Toosendan Fructus-induced hepatotoxicity through IL6,TNF,HSP90AA1,PPARG,PTGS2,HMOX1,and other targets,possibly via the activation of cysteine-type endopeptidase activity involved in these pathways.
文摘The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.
文摘BACKGROUND Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage.We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation.This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma.CASE SUMMARY A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day.She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma.She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure,hepatic failure,and hemodynamic instability,known as toxic liver syndrome.In the setting of uncontrolled hemorrhage and toxic liver syndrome,a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later.She tolerated the anhepatic stage well,and has done well over one year later.CONCLUSION When toxic liver syndrome is recognized,liver transplantation with or withouthepatectomy should be considered before the patient becomes unstable.
文摘The incidence of inflammatory bowel diseases(IBD)is rising worldwide.The therapeutic options for IBD are expanding,and the number of drugs with new targets will rapidly increase in coming years.A rapid step-up approach with close monitoring of intestinal inflammation is extensively used.The fear of side effects represents one the most limiting factor of their use.Despite a widespread use for years,drug induced liver injury(DILI)management remains a challenging situation with Azathioprine and Methotrexate.DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies.The aim of this review is to report incidence,physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.
文摘Inflammatory bowel diseases(IBD)are associated with various hepatobiliary disorders.They can occur at any moment in the course of the disease or associated with the treatment.The prevalence of liver dysfunction can reach up to 50%in different studies.Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD,while primary sclerosing cholangitis is the most specific.Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists.The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD,associated diseases or to the therapies used.
基金supported by China Agriculture Research System (No.CARS-46)the Central Public-interest Scienti?c Institution Basal Research Fund,CAFS (No.YFI202208)the National Natural Science Foundation of China (Nos.31872554and 32172952)
文摘Microplastics(MPs)have become a significant concern for their potential toxicity.However,the correlation between the size of plastic particles and their toxicity remains inconclusive.Here,we investigate the toxic effects of different sizes(80 nm,800 nm,8μm and 80μm)polystyrene MPs(PS-MPs)on the model organism Nile tilapia(Oreochromis niloticus).The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body.H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group.Ed U labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group.The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group.The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group.In conclusion,this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity.All the above lay the foundation for further study on the pathological damage of MPs to other organisms.
基金supported by the National Key Research and Development Program of China(Nos.2020YFA0908000 and 2022YFC2303600)the Guangdong-Dongguan Joint Fund Regional Cultivation Project(No.2021B1515140033)+7 种基金the Dongguan Science and Technology of Social Development Program(No.20221800905732)the National Natural Science Foundation of China(Nos.82074098,82374063,82274182,81841001,and 82173914)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases),Shenzhen Science and Technology Innovation Commission(Nos.JCYJ20220818102613029,JCYJ20210324114014039,and JCYJ20210324115800001)Guangdong Basic and Applied Basic Research Foundation(No.2020A1515110549)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202002)Shenzhen Governmental Sustainable Development Fund(No.KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases(No.ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(No.SZGSP001).
文摘The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely distributed in eutrophic waters.MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals.However,the underlying mechanisms of MCLR-induced liver toxicity are unclear.Herein,we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice.We established the first single-cell atlas ofmouse livers in response to MC-LR.Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treatedwith MC-LR are highly heterogeneous.Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3,which potentially contributed to hepatocyte apoptosis in response to MC-LR.Moreover,MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes.Furthermore,the MC-LR increased several subtypes of CD8+T cells with highly expressed multiple cytokines and chemokines.Overall,apart from directly inducing hepatocytes apoptosis,MC-LR activated proinflammatory Kupffer cell and CD8+T cells,and their interaction may constitute a hostile microenvironment that contributes to liver injury.Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.
基金supported by National Natural Science Foundation of China(Nos.81273569,81001465)Natural Science Foundation of Jiangsu Province,China(No.BK2012726)the Ph.D. Programs Foundation of Ministry of Education of China(No.20100091120028)
文摘Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.
文摘The development of molecular medicine has greatly promoted the research and development (R&D) of innovative drugs. However,drug design and development for those novel targets remains a big challenge with low success rates and high attrition of drug candidates1. The current methodology of new drug R&D is deeply influenced by the idea of allopathic medicine, which directly inhibits biological targets.
文摘Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer,supported by favorable outcomes and good tolerance.However,it is linked to multiple immune manifestations,referred to as immune-related adverse events(irAEs).These adverse events frequently affect the skin,colon,endocrine glands,lungs,and liver.The gastrointestinal system is one of the most commonly affected organ systems and is responsible for the most frequent emergency visits resulting from irAEs.However,because immune checkpoint inhibitors are a recent addition to our arsenal of cancer drugs,many health-care providers remain unfamiliar with the management of irAEs.Gastroenterologists involved in the treatment of oncology patients who have received checkpoint inhibitors are currently encountering cases of abdominal pain,diarrhea,and other nonspecific symptoms that may be challenging to manage.This article reviews the gastrointestinal,hepatic,and pancreatic toxicities of checkpoint inhibitors and provides an approach to their diagnosis and recommended workup.It also highlights the management of irAEs according to their toxicity grading and specifically discusses the instances in which corticosteroids should be administered and/or the immune checkpoint inhibitors should be withheld.