kutkin and Chemical-and-Drug-Induced-Liver-Injury

Oxidative stress is implicated as a common pathologic mechanism contributing to the initiation and progression of hepatic damage in a variety of liver disorders. Present study attempts to evaluate the hepatoprotective activity of picroliv, curcumin and ellagic acid in comparison to silymarin using paracetamol (PCM) induced acute liver damage. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg) and was assessed by quantifying the serum enzyme activities, phenobarbitone induced sleeping time and histopathological analysis of liver tissues. The antioxidant parameters, malondialdehyde (MDA), reduced glutathione (GSH) and catalase of the liver tissue were also assessed. The herbal drugs were administered for 7 days by oral route at 50 and 100 mg/kg. PCM induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase) in serum and MDA level in liver. There was also a significant decrease in activity of GSH and catalase levels. The histopathological examination on toxic models revealed centrizonal necrosis and fatty changes. Pretreatment of mice with picroliv, curcumin and ellagic acid reversed these altered parameters towards normal values, which were compared with silymarin. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver cytochrome P450 enzymes. This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing the lipid peroxidation and augmenting the antioxidant defense system or regeneration of hepatocytes. These active phytochemicals may be developed as drugs for the treatment of liver diseases.

Topics: Acetaminophen; Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cinnamates; Curcumin; Ellagic Acid; Female; Glycosides; Lipid Peroxidation; Liver; Male; Mice; Oxidative Stress; Phytotherapy; Silymarin; Sleep; Vanillic Acid

The potential of Picroliv, a herbal extract against acute cadmium (Cd) intoxication, was evaluated in male rats. Biochemical and histopathological profile in rats pretreated with Picroliv (12 mg/kg, oral) followed by a single dose of Cd as cadmium chloride (CdCl2) (3 mg/kg, ip) revealed marked suppression of oxidative stress in liver and testes. The Cd-induced enhanced levels of lipid peroxidation, membrane fluidity and reduced levels of nonprotein sulphydryls and Na(+)K(+)ATPase were significantly restored to near normal by Picroliv pretreatment. In addition, the Cd-induced serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma glutamyl transpeptidase and lactate dehydrogenase were restored to near basal levels. Hepatic and testicular histopathological damage was also minimized. The results strongly suggest definite hepato- and testicular protection by Picroliv. The antioxidant potential of the herbal extract in the major part, and not its chelating property, seems to be responsible for its ameliorative action.

Topics: Animals; Cadmium Chloride; Chemical and Drug Induced Liver Injury; Cinnamates; Glycosides; Kidney; Liver; Liver Diseases; Male; Malondialdehyde; Oxidative Stress; Rats; Sodium-Potassium-Exchanging ATPase; Sulfhydryl Compounds; Testis; Vanillic Acid

Administration of aflatoxin B1 to rats (2 mg/kg intraperitoneally) caused significant increase in the activities of gamma-glutamyl transpeptidase, 5'-nucleotidase, acid phosphatase, acid ribonuclease as well as content of lipid peroxides in liver after six weeks. However, the activities of succinate dehydrogenase, glucose-6-phosphatase, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase in liver were decreased. The levels of glycogen and reduced glutathione were also decreased. There were significant elevations in the levels of serum transaminases, phosphatases (acid and alkaline), dehydrogenases (sorbitol, lactate and glutamate) and bilirubin following aflatoxin B1 administration. Picroliv (25 mg/kg/day orally for six weeks), an iridoid glycoside isolated from the roots and rhizomes of Picrorhiza kurroa, significantly prevented the biochemical changes induced by aflatoxin B1.

Topics: Aflatoxin B1; Animals; Chemical and Drug Induced Liver Injury; Cinnamates; Drug Interactions; Enzymes; Glutathione; Glycogen; Glycosides; Lipid Peroxidation; Liver; Male; Plant Extracts; Rats; Rats, Wistar; Vanillic Acid

Single doses of aflatoxin B1 (2 mg/kg, i.p.) caused significant increases in the activities of tau-glutamyl transpeptidase, 5'-nucleotidase, acid phosphatase and acid ribonuclease, and decreases in the activities of succinate dehydrogenase and glucose-6-phosphatase in liver, after 8 weeks. The level of lipid peroxides, DNA, RNA, and cholesterol increased while glycogen decreased. It also increased the serum level of transaminases, sorbitol dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, acid phosphatase, alkaline phosphatase, and bilirubin. Oral administration of picroliv (25 mg/kg/day for 15 days), a standardised iridoid glycoside fraction of Picrorhiza kurroa, 6 weeks after aflatoxin B1 toxication, significantly prevented the biochemical changes induced in liver and serum of aflatoxin B1 treated rats. The hepatocurative effect of picroliv and silymarin, a plant based standard hepatoprotective are comparable.

Topics: Aflatoxin B1; Animals; Chemical and Drug Induced Liver Injury; Cinnamates; Glycosides; Male; Rats; Silymarin; Vanillic Acid

Picrorhiza kurrooa (Pk) has been used in liver diseases in the Indian indigenous system of medicine. We undertook this study to determine whether Pk extract possesses hepatoprotective function and if so to determine its nature and mechanism.. Liver injury was induced in 16 mice by thrice-a-week injection of carbon tetrachloride (CCl4) for nine weeks. Eight of them were given daily feeding of Pk extract (12 mg/Kg) 10 days prior to CCl4 injection. Control mice (n = 6) were injected with olive oil for the same period. Serum markers of liver injury and histology of liver tissues were studied. Hepatic glutathione (GSH), total thiol (-SH), glucose 6-phosphate dehydrogenase (G6PD), catalase, lipid peroxidation and plasma membrane-bound Na+/K+ ATPase were also determined.. CCl4 treatment resulted in significant elevation of serum ALT and AST. Liver GSH [6.3 (0.7) vs control 10.5 (1.1) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ AT-Pase [164.3 (23.2) vs control 358.4 (12.9) nmole pi released/min/mg protein] were significantly reduced. Significant increase of lipid peroxidation [3.0 (0.6) vs control 1.0 (0.3) nmole MDA/mg protein] and histologic changes characteristic of liver injury were also seen. Feeding of Pk extract in CCl4-treated mice caused significantly less alteration of serum ALT, AST, liver GSH [8.9 (0.7) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ ATPase [270.8 (21.3) nmole pi released/min/mg protein]. Histologic lesions of liver and lipid peroxidation [1.7 (0.4) nmole MDA/mg protein] were also significantly less in these animals.. The extract of Pk appears to offer significant protection against liver damage by CCl4. It probably acts as free-radical scavenger and inhibitor of lipid peroxidation of liver plasma membrane.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cinnamates; Glycosides; Mice; Mice, Inbred BALB C; Plant Extracts; Vanillic Acid

Topics: Chemical and Drug Induced Liver Injury; Cinnamates; Glycosides; Humans; Liver; Plant Extracts; Plants, Medicinal; Silymarin; Vanillic Acid

Picroliv, a standardized extract from the plant Picrorhiza kurrooa containing active constituents, showed a significant dose dependent (3-12 mg/kg p.o. x 7) protective activity against galactosamine-induced hepatic damage in rat as evaluated on the isolated hepatocytes (ex vivo) preparation. It markedly increased the percentage of viability of hepatocytes. It also restored the galactosamine-induced changes in the levels of enzymes (GOT, GPT and alkaline phosphatase) both in isolated hepatic cells as well as in serum. In addition, picroliv possessed a marked anticholestatic effect. Picroliv was found to be more potent than silymarin, a standard hepatoprotective agent.

Topics: Animals; Bile; Chemical and Drug Induced Liver Injury; Cinnamates; Female; Galactosamine; Glycosides; In Vitro Techniques; Liver Diseases; Male; Plant Extracts; Rats; Silymarin; Vanillic Acid

The efficacy of Picroliv, a standardized iridoid glycoside fraction of Picrorhiza kurroa, was studied against the Amanita phalloides-induced biochemical changes in rat liver. A phalloides (50 mg.kg-1) caused significant increases in the activities of hepatic 5'-nucleotidase, gamma-glutamyl transpeptidase, acid ribonuclease, and succinate dehydrogenase, but a decrease in glucose-6-phosphatase. The level of cytochrome P-450 in microsomal fraction and content of glycogen in liver showed significant depletions. Picroliv (25 mg.kg-1.d-1 x 10 d) provided significant restorations of all the biochemical changes poisoned by A phalloides except cytochrome P-450 and glycogen. These results demonstrated the protective effect of Picroliv against A phalloides-induced hepatotoxicity in rats.

Topics: Amanita; Animals; Chemical and Drug Induced Liver Injury; Cinnamates; gamma-Glutamyltransferase; Glycosides; Liver Glycogen; Male; Mushroom Poisoning; Oxidoreductases; Phosphoric Monoester Hydrolases; Rats; Rats, Inbred Strains; Vanillic Acid

The hepatoprotective activity of picroliv, the irridoid glycoside mixture from Picrorhiza kurrooa, was determined in adult male albino rats. Pretreatment with picroliv prevented the hepatotoxic effects of paracetamol and galactosamine as evidenced by various biochemical and histopathological observations. Maximum hepatoprotective effect was observed with daily oral doses of 6 and 12 mg/kg for 7 or 8 days. The antihepatotoxic action of picroliv seems likely due to an alteration in the biotransformation of the toxic substances resulting in decreased formation of reactive metabolites.

Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury; Cinnamates; Galactosamine; Glycosides; India; Liver; Liver Function Tests; Male; Plant Extracts; Plants, Medicinal; Rats; Rats, Inbred Strains; Silymarin; Vanillic Acid

Monocrotaline, a pyrrolizidine alkaloid, caused changes in most of the biochemical parameters in rats 12 days after a single dose of 120 mg/kg. These included significantly increased activities of hepatic succinate dehydrogenase, acid ribonuclease, acid phosphatase, gammaglutamyl transpeptidase and 5'-nucleotidase and decreased in the activities of glucose-6-phosphatase and cytochrome P450. The levels of DNA, RNA and glycogen in liver and albumin and protein in serum decreased while serum bilirubin increased. The histopathological changes in liver were characterized by diffused hepatocyte alterations in the form of ballooning, granular cytoplasm, indistinct cell outlines, nuclear changes, focal necrosis, and vascular damage. When picroliv, a standardized iridoid glycoside fraction of Picrorhiza kurroa, was administered orally in a dose of 25 mg/kg simultaneously with monocrotaline, alterations in most of the biochemical parameters along with the histopathological changes in liver caused by monocrotaline were prevented.

Topics: Animals; Chemical and Drug Induced Liver Injury; Cinnamates; Glycosides; Liver Diseases; Male; Monocrotaline; Plant Extracts; Pyrrolizidine Alkaloids; Rats; Rats, Inbred Strains; Vanillic Acid

Thioacetamide (100 mg/kg), when administered to normal rats, caused a significant increase in the activities of 5'-nucleotidase and gamma-glutamyl transpeptidase and a decrease in the activities of glucose 6-phosphatase and succinate dehydrogenase enzymes in the liver. DNA, RNA, and proteins were increased while the cytochrome P450 in the microsomal fraction and the glycogen content in the liver were decreased significantly. Elevations in the activities of GOT, GPT, and alkaline phosphatase and bilirubin content in serum were also observed. Picroliv, a standardised glycoside fraction of Picrorhiza kurroa, in doses of 12.5 and 25 mg/kg prevented most of the biochemical changes induced by thioacetamide in liver and serum. The hepatoprotective activity of Picroliv was comparable with that of silymarin, a known hepatoprotective agent obtained from seeds of Silybum marianum.

Topics: Animals; Chemical and Drug Induced Liver Injury; Cinnamates; Glycosides; Liver Diseases; Male; Rats; Rats, Inbred Strains; Silymarin; Thioacetamide; Vanillic Acid