stigmasterol and Chemical-and-Drug-Induced-Liver-Injury

Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported.. We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil-based lipid emulsions.. Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4-fold to 5.6-fold higher in PN-dependent patients ( P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol ( r = 0.83-0.89, P = .02-.04), while serum and liver total PS levels were positively interrelated ( r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN-dependent patients. All liver PS fractions correlated positively with histologic portal inflammation ( r = 0.53-0.66, P < .05), and their total concentration was significantly ( P = .01) higher among patients with versus without portal inflammation. In PN-dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels ( r = 0.79-0.87, P ≤ .03).. Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholesterol; Female; gamma-Glutamyltransferase; Humans; Infant; Inflammation; Intestinal Diseases; Liver; Male; Parenteral Nutrition; Phytosterols; Plant Oils; Portal Vein; Sitosterols; Stigmasterol; Triglycerides

Fucosterol is the primary sterol found in brown algae. Recently, considerable interest has been generated regarding fucosterol due to its potential antioxidant, anti-inflammatory and antidiabetic effects. The aim of this study was to investigate the protective effects of fucosterol on tert-butyl hydroperoxide (t-BHP)- and tacrine-induced oxidative stress in HepG2 cells.. Fucosterol by itself exhibited no cytotoxicity at concentrations below 100 μm by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The increased intracellular reactive oxygen species (ROS) and decreased glutathione levels observed in t-BHP- and tacrine-treated HepG2 cells were ameliorated by fucosterol pretreatment, indicating that the protective effects of fucosterol are mediated by the induction of cellular defence mechanisms against oxidative stress. Moreover, elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in tacrine-treated mice were significantly reduced after oral administration of fucosterol.. The hepatoprotective effects of fucosterol may occur via an increase in the hepatic level of glutathione and a decrease in ROS production, thereby preventing hepatic damage and the resultant increases in ALT and AST activity.. These results suggest that fucosterol may be an effective hepatoprotective agent that could be useful for preventive therapies against oxidative stress-related hepatotoxicity.

Topics: Animals; Cell Survival; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione; Hep G2 Cells; Humans; Male; Mice; Oxidative Stress; Phaeophyceae; Protective Agents; Reactive Oxygen Species; Stigmasterol; Tacrine; tert-Butylhydroperoxide

The present study was designed to evaluate the hepatoprotective effects of newly isolated stigmast-4, 20 (21), 23-trien-3-one (STO) against carbon tetrachloride-induced hepatic injury in Wistar albino rats. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl4 (0.5 mL/kg CCl4 in olive oil) in experimental rats. Three different doses (2.5, 5.0, and 10 mg/kg, p.o) of STO was administered to the test groups during whole experimental protocol. Changes in the activity of serum ALT, AST, ALP, TB, and TP, anti-oxidant enzymes like SOD, CAT, GPx, GST, and LPO were studied in CCl4-induced hepatocellular carcinogenesis. The altered levels of serum ALT, AST, ALP, TB, and TP restored toward normalization significantly by STO in a dose dependant manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, it also produced a significant and dose-dependent reversal of CCl4-diminished activity of anti-oxidant enzymes like SOD, CAT, GPx, GST, and the reduced CCl4-elevated level of LPO. STO significantly prevented the increased levels of serum markers, also suppressed the free radical processes by scavenging hydroxyl radicals. It also modulates the levels of LPO and markedly increases the endogenous anti-oxidant enzymes level in CCl4-induced hepatic injury.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bilirubin; Biomarkers; Carbon Tetrachloride; Catalase; Chemical and Drug Induced Liver Injury; Drug Evaluation, Preclinical; Glutathione Peroxidase; Glutathione Transferase; Liver; Rats; Rats, Wistar; Stigmasterol; Superoxide Dismutase

The anti-oxidant activities of fucosterol isolated from the marine algae Pelvetia siliquosa were investigated. Fucosterol exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats. Fucosterol inhibited the sGOT and sGPT activities by 25.57 and 63.16%, respectively. Fucosterol showed the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities by 33.89, 21.56 and 39.24%, respectively, in CCl4-intoxicated rats. These results suggest that fucosterol possess not only the anti-oxidant, but also the hepatoprotective activities in rats.

Topics: Administration, Oral; Animals; Antioxidants; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Catalase; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Drug Administration Schedule; Eukaryota; Glutathione Peroxidase; Hexanes; Injections, Intraperitoneal; Korea; Liver; Male; Plant Extracts; Premedication; Rats; Rats, Sprague-Dawley; Silymarin; Stigmasterol; Superoxide Dismutase; Transaminases

To study the pharmacologically active components of Eclipta prostrata.. The components were extracted by alcohol and isolated by silica gel column and subjected to pharmacological screening.. Four compounds were isolated from E. prostrata, of which two were identified as stigmasterol and alpha-terthienyl.. alpha-Terthienyl was isolated from the plant for the first time. The EtOAc part of alcoholic extraction exhibits significant hepatoprotective activity against carbon terachloride-induced liver injury in rats.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Asteraceae; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Drugs, Chinese Herbal; Mice; Plants, Medicinal; Random Allocation; Stigmasterol