PubMed · 14096777
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Y HAYASHI. 1963. [ON LIVER FUNCTION TESTS].. https://pubmed.ncbi.nlm.nih.gov/14096777/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Oxidative stress is involved in the pathogenesis of chemically mediated liver injury. Since glycosaminoglycans possess antioxidant activity, the aim of this work was to assess the protective effects of hyaluronic acid and chondroitin-4-sulphate treatment in a model of carbon tetrachloride-induced liver injury. Liver damage was induced in male rats by an intraperitoneal injection of carbon tetrachloride (1 ml/kg in vegetal oil). Serum alanine aminotransferase and aspartate aminotransferase, hepatic malondialdehyde, plasma TNF-alpha, hepatic reduced glutathione and catalase, and myeloperoxidase, an index of polymorphonuclear infiltration in the jeopardised hepatic tissue, were evaluated 24 h after carbon tetrachloride administration. Carbon tetrachloride produced a marked increase in serum alanine aminotransferase and aspartate aminotransferase activities, primed lipid peroxidation, enhanced plasma TNF-alpha levels, induced a severe depletion of reduced glutathione and catalase, and promoted neutrophil accumulation. Intraperitoneal treatment of rats with hyaluronic acid (25 mg/kg) or chondroitin-4-sulphate (25 mg/kg) failed to exert any effect in the considered parameter, while the combination treatment with both glycosaminoglycans (12,5 + 12,5 mg/kg) decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, inhibited lipid peroxidation by reducing hepatic malondialdehyde, reduced plasma TNF-alpha, restored the endogenous antioxidants, and finally decreased myeloperoxidase activity. These results suggest that hyaluronic acid and chondroitin-4-sulphate possess a different antioxidant mechanism and consequently the combined administration of both glycosaminoglycans exerts a synergistic effect with respect to the single treatment.
This study investigated the protective effects of acteoside, a phenylethanoid glycoside, on the carbon tetrachloride-induced hepatotoxicity as well as the possible mechanisms involved in this protection in mice. Pretreatment with acteoside prior to the administration of carbon tetrachloride significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with acteoside significantly prevented the increase in hepatic malondialdehyde formation and the depletion of the reduced glutathione content in the liver of carbon tetrachloride-intoxicated mice. Carbon tetrachloride-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of acteoside on cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were also investigated. Treatment of the mice with acteoside resulted in a significant decrease in the P450 2E1-dependent pnitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2El protein levels were also lower. Acteoside exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity. These results suggest that the protective effects of acteoside against the carbon tetrachloride-induced hepatotoxicity possibly involve mechanisms related to its ability to block the P450-mediated carbon tetrachloride bioactivation and free radical scavenging effects.
BACKGROUND: Viral hepatitis and autoimmune liver diseases cause hepatocyte apoptosis. Concanavalin A (Con A)-induced hepatitis resembles human viral hepatitis and autoimmune hepatitis. The role of nitric oxide (NO) in liver injury was controversial in different liver injury models. We hypothesize both endogenous and exogenous NO protect liver against Con A-induced liver injury. Molsidomine is metabolized into SIN-1 by the liver, and SIN-1 subsequently generates NO. So, molsidomine was used as a NO donor in this study. STUDY DESIGN: To study a protective role of endogenous NO in Con A-induced liver injury, mice were pretreated with a specific inducible nitric oxide synthase (iNOS) inhibitor, L-N(6)-(1-iminoethyl)-lysine (L-NIL), before Con A challenge. To study a time-dependent protection against Con A-induced liver injury, animals were either given molsidomine, a NO donor, before or after Con A administration. Serum alanine aminotranferase (ALT) was analyzed. Liver samples were subjected to DNA fragmentation assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling stain, Western blot analysis, and caspase activity assays. RESULTS: Animals pretreated with L-NIL had significantly increased serum ALT levels compared with those challenged with Con A alone; but pretreatment with molsidomine dramatically decreased ALT levels in L-NIL-pretreated animals or in animals that received Con A alone. Administration of molsidomine 30 minutes before or 1, 2, and 3 hours after Con A injection significantly reduced serum ALT levels and attenuated hepatocyte apoptosis from caspase inactivation. The ALT reduction was associated with inhibition of both caspase-3 and caspase-8 activation and reduction of hepatocyte apoptosis. CONCLUSIONS: Endogenous NO plays an important protective role against Con A-induced liver injury by reducing hepatocyte apoptosis. Administration of a NO donor early after Con A injection protects the liver from injury. This is the first study demonstrating a time-dependent inhibition of liver injury induced by Con A administration.