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.
Fu
Y
Y
Department of Animal Science, Cornell University, Ithaca, New York 14853, USA.
Cheng
W H
WH
Ross
D A
DA
Lei
X g
Xg
D000818:Animals; D002374:Catalase / Q000378:metabolism; D004178:Diquat / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012643:Selenium / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D004178:Diquat; D002374:Catalase; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse