The present study was undertaken to determine whether d galactosamine d galn induces ali via the mitochondrial apoptosis and proinflammatory cytokinesignaling pathways, and possible mechanisms by which green tea gt extract modulates the apoptotic and proinflammatory signaling in rat. Liver damage was induced by intra peritoneal administration of 400 mgkg b wt d galactosamine on the last day. Normoactive smooth endoplasmic reticulum and modification by phenobarbital raymond s. Hepato protective activity of various extracts of indigofera. Ameliorative effect of ethanolic extract of roots of. Druginduced hepatotoxicity and hepatoprotective medicinal. Effect of lecithin on d galactosamine induced hepatotoxicity. Sirt1 modulators in experimentally induced liver injury. Treatment with boswellia ovalifoliolata root extracts has protected liver from induced hepatotoxicity. Hepatoprotective activity of lepidium sativum seeds against d. Mar 25, 2009 oxidative stress and inflammation contributed to the propagation of acute liver injury ali. Plasma total triglycerides tg, total cholesterol, high density lipoprotein cholesterol hdlc, low density lipoprotein cholesterol ldl.
Drugs that induce hepatotoxic effects in mammals were injected into the silkworm. The role of endotoxin in liver injury induced by d galactosamine galn was investigated in rats in vivo, or by using isolated rat hepatocytes in vitro. Dgalactosamine is an amino sugar derivative of dgalactose item no. Pdf hepatoprotective activity of dypsis lutescens against d. Green tea extract supplement reduces dgalactosamineinduced. In this study, danhong injection dhi was investigated to evaluate the preventive and protective effect on ahf induced by lipopolysaccharide lps and dgalactosamine galn in mice. In this study, danhong injection dhi was investigated to evaluate the preventive and protective effect on ahf induced by lipopolysaccharide lps and d galactosamine galn in mice. Dgalactosamine lipopolysaccharide induced acute liver injury in mice via increased production of tnf. Forty male spraguedawley rats were divided into normal control, galn control, a. Liver injury markers exhibited an inverse relationship with sirt1 expression. The hepatoprotective effects of acetylbergenin were examined against dgalactosamine galninduced liver damage in rats, compared with that of bergenin reported previously. Full text pdf 1764k abstracts references20 citedby5 the role of endotoxin in liver injury induced by dgalactosamine galn was investigated in rats in vivo, or by using isolated rat hepatocytes in vitro. D galactosamine is hepatotoxic and is used, alone or in combination with lps, as a model of liver failure in rodents. Sirt1 resveratrol ex527 dgalactosamine lipopolysaccharide hepatotoxicity corresponding author m.
Modulation of dgalactosaminelipopolysacharrideinduced. Pdf hepatoprotective effect of pentoxifylline against d. Xu yang1, masayoshi fujisawa1, teizo yoshimura1, toshiaki ohara1, miwa sato1, megumi mino1, thar htet san1, tong gao1, steven l. The selective sirt1 modulators whether activators stacs or inhibitors are being tried experimentally and clinically. Dgalactosamine galn is a hepatotoxin frequently used in the study of liver injury 1. Dietary glycine or pretreatment with gdcl 3 prevented these effects. Dgalactosaminelipopolysaccharideinduced hepatotoxicity. Apoptotic, hepatoprotective and antioxidant potential of a triherbal formulation against dgalactosamine hepatotoxicity 2 introduction the liver is the primary site for drug metabolism therefore hepatotoxicity is one of the most frequently reported human adverse drug reactions. The protective effect of pinitol against dgalactosamine galninduced liver damage was examined. Sabesin medical service, boston veterans administration hospital, and the department of medicine, boston university school of medicine.
This article is directed at highlighting the involvement of the endogenous stress sensor sirt1 silent information regulator t1 as a possible factor involved in hepatoprotection. Hepatoprotective activity of lepidium sativum seeds against dgalactosamine lipopolysaccharide induced hepatotoxicity in animal model. To isolate and identify the polyphenolic constituents of. Male c57bl6 mice aged 68 weeks were randomized into three groups. Sixth conference of the world day for research, riyadh, 2014. The present study was aimed to evaluate the hepatoprotective activity of ethanolic extract of roots of tetracera akara root on dgalactosamine induced hepatotoxicity in wistar rats. Aug 23, 2011 twenty four wistar strain albino rats were used for the investigations. Effect of chrysin on hepatoprotective and antioxidant. D galactosamine induced utp deficiency is reversed completely within 90 min after uridine administration.
Protective effect of danhong injection on acute hepatic. Conclusion the eeib found to have significant hepatoprotective activity by dgaln induced. Hepatoprotective effect of pentoxifylline against dgalactosamine induced hepatotoxicity in rats. Our previous studies suggest silkworms can be used as model animals instead of mammals in pharmacologic studies to develop novel therapeutic medicines. Fourth international conference on clinical nutrition and community nutrition, riyadh, 2008. Liver damage was induced by intra peritoneal administration of 400 mgkg b wt dgalactosamine dgaln.
Modification of the hepatotoxicity of d galactosamine in the rat by cycloheximide. The hepatoprotective effects of acetylbergenin were examined against dgalactosamine galn induced liver damage in rats, compared with that of bergenin reported previously. Request pdf effect of chrysin on hepatoprotective and antioxidant status in dgalactosamineinduced hepatitis in rats chrysin is a natural, biologically active compound present in many plants. Curcumin, a naturally occurring antioxidant, has various beneficial effects in the treatment of human diseases. Biochemical data exhibited significant hepatoprotective activity of methanol extract of portulaca oleracea at oral dose of 200 and 400 mgkg against dgalactosamine. Attenuation of oxidative stress and hepatotoxicity induced by d. Curcumin attenuates dgalactosaminelipopolysaccharide. We discuss the modulation of sirt1 on cytoprotection or even cytotoxicity in the liver chemically. Modification of the hepatotoxicity of dgalactosamine in the. Pretreatment with eeib and silymarin for 21days protected the rat livers from dgalactosamine induced hepatotoxicity. When lipid emulsion was applied immediately after d galactosamine, the. The aim of the present wok the hepatoprotective activity as well as the antioxidant potential of the ethyl acetate stem extract of m. However, little information regarding the protection it provides against acute liver. However, treatment with silymarin and liv52 significantly decrease the biochemical markers, as compared to d galactosamine group.
Luteolin and luteolin7oglucoside protect against acute liver injury through regulation of inflammatory mediators and antioxidative enzymes in galnlpsinduced hepatitic icr mice chung mu park, 1 and youngsun song 2. The efficacy of dietary spirulina as an adjunct to. D galactosamine exerts its hepatotoxicity by causing intracellular deficiency of uridine metabolites, presumably in conjunction with other factors such as endotoxinaemia 66. This was demonstrated by reducing the elevated levels of biochemical markers and additional histopathological observations have shown that there is an improvement in the structural design of liver due to induced hepatotoxicity. The aim of this study was to assess dgalactosamine dgalnlipopolysaccharide lpsinduced hepatocyte apoptotic changes in mice and clarify the mechanisms involved in this process. We examined the usefulness of the silkworm larvae bombyx mori as an animal model for evaluating tissue injury induced by various cytotoxic drugs. Hepatobiliary clearance of labelled mebrofenin in normal and d galactosamine hcl induced hepatitis rats and the protective effect of turmeric extract. Oxidative stress and inflammation contributed to the propagation of acute liver injury ali. Lead optimization strategies to improve potency, efficacy, metabolic stability, and. Dgalactosamine hydrochloride cas 1772038 cayman chemical. Warning this product is not for human or veterinary use. Antiinflammatory, antioxidant and antihepatotoxic effects of spirulina platensis against dgalactosamine induced hepatotoxicity in rats. Hepatoprotective effects of il22 on fulminant hepatic failure induced by dgalactosamine and lipopolysaccharide in mice. However, overactivation thereof may lead to hepatocellular damage.
Original article picroside ii ameliorates acute liver. Molecular mechanisms of dgalactosaminelipopolysaccharide. Additionally, antisera to tumor necrosis factor tnf prevented hepatotoxicity caused byd. Kemelo, institute of pharmacology, first faculty of medicine, charles university in prague, albertov 4, 128 00 prague 2, czech republic. Liver transplant for viral hepatitis and fulminant hepatic failure. Original article picroside ii ameliorates acute liver injury. Selective uridine triphosphate deficiency induced by d.
Liver injury induced by d galn has been used as the animal model for liver injury, since its morphological and pathophysiological characteristics are similar to those of human hepatits b. Hepatotoxicity was induced in wistar rats by intraperitoneal injection of dgaln 400 mgkg in saline in wistar rats. D galactosamine is observed only when a low dose of endotoxin is also administered,10 causing activation of kupffer cells and tumor necrosis factora tnfa release. In colectomized rats, galn produced little hepatotoxicity, while it induced severe liver damage by simultaneous administration of. The animals were divided into four groups of six animals in each group. Hepg2 cell lines were used for in vitro study and dgalactosamine dgaln. The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Modification of the hepatotoxicity of dgalactosamine in. The present study was aimed to evaluate the hepatoprotective activity of ethanolic extract of roots of tetracera akara root on d galactosamine induced hepatotoxicity in wistar rats. Effect of lecithin on dgalactosamine induced hepatotoxicity. Discovery and optimization of a novel triazole series of. Galactosamine definition of galactosamine by medical. Pdf curcumin attenuates dgalactosaminelipopolysaccharide. Evaluation of druginduced tissue injury by measuring.
Isoproterenol induced myocardial infarction in male wistar rats aristatile balakrishnan king saud university, saudi arabia title. Ambrex was orally administered for a period of 7 days at dose levels of 250 and 500 mgkg b. Research article open access evaluation of hepatoprotective. Glycine and uridine prevent dgalactosamine hepatotoxicity in the rat. Effect of chrysin on hepatoprotective and antioxidant status. Modification of the hepatotoxicity of dgalactosamine in the rat by cycloheximide. Drug induced hepatotoxicity is the leading cause of acute liver failure. Nature and mechanisms of hepatocyte apoptosis induced by d. Acute hepatic failure ahf, which leads to an extremely high mortality rate, has become the focus of attention in clinic. Liver damage was induced by intra peritoneal administration of 400 mgkg b wt d galactosamine d galn. Thirty sex and age matched normal subjects were included as controls. Manual of histology, staining methods of armed forces, institute of pathology.
Liver damage was induced by intra peritoneal administration of 400 mgkg b wt dgalactosamine on the. The combination of lps and dgalactosamine galn is used experimentally to induce acute liver injury similar to fhf observed clinically. Our data showed a high increase of serum aminotransferases after d galactosamine administration, which indicates a high extent of liver injury. Hepatotoxic effect of dgalactosamine and protective role of. Protective effect of pinitol against d galactosamineinduced. Green tea extract supplement reduces dgalactosamine. The appearance of d galactosamine induced hepatitis and generalized edema in. Experimental and molecular pathology 19, 168177 1973 dgalactosamine hepatotoxicity iii.
A combination of d galactosamine and lipopolysaccharide d galnlps downregulated sirt1 expression, while sirt1 activators, srt1720, resveratrol, and quercetin, upregulated sirt1 and alleviated d galnlps induced acute hepatotoxicity. A class of triazole gpr142 agonists was discovered through a high throughput screen. At the end of the study animals were sacrificed and liver enzyme levels, histopathology, mitochondrial integrity, expression of p53, bax. Drugs that induce hepatotoxic effects in mammals were injected into the silkworm hemocoel, and. Dgalactosamine induced hepatic damage was manifested by a significant increase in the activities of marker enzymes. Acetylbergenin was administered orally once daily for 7 days and then galn. Dgalactosamine exerts its hepatotoxicity by causing intracellular deficiency of uridine metabolites, presumably in conjunction with other factors such as endotoxinaemia 66. Pdf hepatoprotective effect of phyllanthus niruri alkaloid fraction. The hepatoprotective effects of acetylbergenin were examined against d galactosamine galn induced liver damage in rats, compared with that of bergenin reported previously. The ali model was established by intraperitoneal i. The appearance of dgalactosamineinduced hepatitis and generalized edema in.
Effects of dgalactosamineinduced acute liver injury on. Dgalactosamine is hepatotoxic and is used, alone or in combination with lps, as a model of liver failure in rodents. Teas and other beverages suppress dgalactosamine induced liver injury in rats. Nacetyldgalactosamine galnac, an aminosugar, is a component of many olinked and nlinked glycan structures. The present study was undertaken to determine whether dgalactosamine dgaln induces ali via the mitochondrial apoptosis and proinflammatory cytokinesignaling pathways, and possible mechanisms by which green tea gt extract modulates the apoptotic and proinflammatory signaling. Effects of acetylbergenin against d galactosamineinduced. Twenty four wistar strain albino rats were used for the investigations. Dgalactosamine induces fulminant liver failure by intraperitoneal injection in doses of 200 mgkg 67. Predicted data is generated using the us environmental protection agencys episuite. Lecithin administration and d galctosamine d galn challenge. Hepatoprotective effect of phyllanthus niruri alkaloid fraction in dgalactosamine induced hepatitis in rats. Hepatobiliary clearance of labelled mebrofenin in normal and dgalactosamine hclinduced hepatitis rats and the protective effect of turmeric extract. Evaluation of druginduced tissue injury by measuring alanine. Effects of resveratrol and ex527 pretreatment in lipopolysaccharide induced hepatitis in d galactosamine sensitized rats d galnlps on plasma levels of alanine aminotransferase alt, aspartate aminotransferase ast a b and bilirubin c.
The lead compound 4 suffered from poor metabolic stability and poor solubility. Sabesin medical service, boston veterans administration hospital, and the department of medicine, boston university school of medicine, boston, massachusetts. Lecithin 50 and 100 mgkg b wt was administered for 1 week by oral route. Glycine and uridine prevent dgalactosamine hepatotoxicity in. Mice received an intraperitoneal injection of 1 25, 50, 100, and 200 mgkg1 1 h before treatment with galn 700 mgkg1lps 10. Treatment of experimental animals with d galactosamine galn lipopolysaccharide lps causes lethal liver injury that is characterized by apoptosis of the hepatocyte. The aim of this study was to assess d galactosamine d galnlipopolysaccharide lps induced hepatocyte apoptotic changes in mice and clarify the mechanisms involved in this process.
Spred2 deficiency exacerbates dgalactosaminelipopolysaccharide induced acute liver injury in mice via increased production of tnf xu. Role of endotoxin in dgalactosamine induced hepatic injury. Pretreatment with eeib and silymarin for 21days protected the rat livers from d galactosamine induced hepatotoxicity. Patients blood samples were collected at both the debut and recovery of diseases. D galactosamine induces fulminant liver failure by intraperitoneal injection in doses of 200 mgkg 67. Comprehensive analysis of differential gene expression. Protective effect of ultrasonicationprocessed ginseng berry extract.
Lecithin administration and dgalctosamine dgaln challenge. In colectomized rats, galn produced little hepatotoxicity, while it induced severe liver damage by simultaneous administration of lipopolysaccharide lps. Comprehensive analysis of differential gene expression pro. However, treatment with silymarin and liv52 significantly decrease the biochemical markers, as compared to dgalactosamine group. Apoptosis plays a role in the normal development of liver. A high dose of galn is known to induce apoptosis of hepatocytes in rat and mouse, which is evidenced by histochemical observations, dna laddering, and caspase 3 activation 24. The protective effect of pinitol against d galactosamine galn induced liver damage was examined. In this study, the protective effects of luteolin 1, a major component of cirsium japonicum were examined against dgalactosamine galnlipopolysaccharide lpsinduced fulminant hepatic failure. Model hepatotoxicants acetaminophen paracetamol acetaminophen also known as paracetamol or. Gpr142 has been identified as a potential glucosestimulated insulin secretion gsis target for the treatment of type 2 diabetes mellitus t2dm.
Protective effect of pinitol against d galactosamine. Pdf hepatoprotective activity of lepidium sativum seeds. We analyzed the molecular mechanism of galnlps induced apoptosis of hepatocytes and examined the therapeutic effects of etoposide on galn lps induced lethal liver injury. Dgalactosamineinduced utp deficiency is reversed completely within 90 min after uridine administration. Apr 24, 2014 mukherjee s, mahmoudi tm and mukherjee u. Thurman1,3 extrahepatic factors, such as increased gut permeability and bacteria from the gut, have been shown to play a role in. D galactosamine is a hepatotoxic agent, which induces diffuse injury of liver tissue followed by the regeneration process.
As udpgalnac, galnac is the intial olinked sugar to many serine and threonine residues in protein glycosylations. This offers the possibility to inhibit utpdependent processes in vivo for periods corresponding to the time interval between galactosamine and uridine injection. Impaired plasma lipid profiles in acute hepatitis lipids. D galactosamine is an amino sugar derivative of d galactose item no. Hepatotoxic effect of dgalactosamine and protective role. Protective effects of luteolin against apoptotic liver damage. We analyzed the molecular mechanism of galnlpsinduced apoptosis of hepatocytes and examined the therapeutic effects of etoposide on galn lpsinduced lethal liver injury. Hepatocellular foci were observed in 2 out of 8 and 6 out of 7 animals in the flpb gal and flfl gal groups, respectively. Hepatotoxicity was induced in wistar rats by intraperitoneal injection of d galn 400 mgkg in saline in wistar rats. Glycine and uridine prevent dgalactosamine hepatotoxicity. Acetylbergenin was synthesized from acetylation of bergenin, isolated from mallotus japonicus, to increase lipophilic and physiological activities. Treatment of experimental animals with dgalactosamine galn lipopolysaccharide lps causes lethal liver injury that is characterized by apoptosis of the hepatocyte. Protective effects of luteolin against apoptotic liver. Liver damage was induced by intra peritoneal administration of 400 mgkg b wt dgalactosamine on the last day.
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