Elevation Of Plasma Alanine Aminotransferase Activity Research Articles

Cellular glutathione peroxidase protects mice against lethal oxidative stress induced by various doses of diquat.

This study was to determine if cellular glutathione peroxidase (GPX1) protects against acute oxidative stress induced by diquat. Lethality and hepatic biochemical indicators in GPX1 knockout mice [GPX1(-/-)] were compared with those of wild-type mice (WT) after an intraperitoneal injection of diquat at 6, 12, 24, or 48 mg/kg of body weight. Although the WT survived all the doses, the GPX1(-/-) survived only 6 mg diquat/kg and were killed by 12, 24, and 48 mg diquat/kg at 52, 4.4 and 3.9 hr, respectively. Compared with those of surviving mice that were sacrificed on Day 7, the dead GPX1(-/-) had diquat dose-dependent increases (P < 0.05) in plasma alanine aminotransferase (ALT) activities. The GPX1(-/-) also had higher (P < 0.05) liver carbonyl contents than those of the WT, but the differences were irrespective of diquat doses. Whereas hepatic total GPX and phospholipid hydroperoxide glutathione peroxidase activities or hepatic GPX1 protein was not significantly affected by the diquat treatment, liver thioredoxin reductase and catalase activities were lower (P < 0.05) in the GPX1(-/-) injected with 12 mg diquat/kg than those of other groups. In conclusion, normal GPX1 expression is necessary to protect mice against the lethality, hepatic protein oxidation, and elevation of plasma ALT activity induced by 12-48 mg diquat/kg.

Comparison of the effects of ascorbyl palmitate and L-ascorbic acid on paracetamol-induced hepatotoxicity in the mouse

The effects of ascorbyl palmitate (ASCP) and free L-ascorbic acid (LAA) on the hepatotoxicity of paracetamol (acetaminophen) and the in vivo covalent binding of reactive paracetamol metabolites to hepatic proteins has been studied in male MF1 mice. The oral administration of [ 3H(G)]paracetamol (600 mg/kg) resulted in covalent binding to hepatic proteins, a depletion of hepatic non-protein sulphydryl (NPS) groups after 2 h, and a marked elevation of plasma alanine aminotransferase (ALAT) activity after 24 h. The coadministration of paracetamol and ASCP (1412 mg/kg), equivalent to 600 mg/ kg free LAA), but not paracetamol and LAA (600 mg/kg), significantly reduced covalent binding of paracetamol metabolites at 2 and 4 h after treatment. In addition ASCP, but not LAA, significantly reduced the depletion of NPS groups and the elevation of plasma ALAT activity. ASCP also completely prevented the 35% mortality observed at 24 h in paracetamol treated mice. These results demonstrate that ASCP, but not LAA, when coadministered orally with the analgesic is an effective inhibitor of paracetamol-induced hepatotoxicity in the mouse. The mechanism by which ASCP prevents liver injury appears to involve destruction of reactive paracetamol metabolites which is associated with a sparing action on hepatic reduced glutathione levels.