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.