7-Hydroperoxycholesterol as a marker of oxidative stress in rat kidney induced by paraquat.
The in vivo paraquat-induced oxidative stress in rat tissue was studied by analyzing cholesterol-derived hydroperoxide as an index of lipid peroxidation. Paraquat (10 mg/kg) was administered i.p. to rats. Rats were sacrificed and lung, liver, and kidney were collected 2, 24 h, and 5 d after paraquat injection. Lipids were extracted and analyzed by HPLC with post-column chemiluminescence. We found that two cholesterol-derived hydroperoxides, 7alpha-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH) and 7beta-hydroperoxycholest-5-en-3beta-ol (7beta-OOH) were present in lungs of control animals (0.06 and 0.06 nmol/g, respectively), in livers (6.5 and 15.8 nmol/g, respectively) and in kidneys (3.7 and 8.9 nmol/g, respectively). In liver paraquat increased lipid peroxidation approximately by 60% over the levels of control animals only at 2 h after paraquat treatment. In kidney, augmented lipid peroxidation, 7alpha-OOH and 7beta-OOH (by 70% and 147%, respectively) above levels was found at 2 h after paraquat treatment. Interestingly, these increase remained in kidney of rats 5 d after a single dose of paraquat. In contrast, cholesterol-derived hydroperoxides were not affected in lung of paraquat dosed rats. This is the first report on 7alpha-OOH and 7beta-OOH accumulations in rat liver and kidney, and it seems to reflect greater oxidative stress in the pathology of kidney of rats treated with acute paraquat at low dose.
Adachi
J
J
Department of Legal Medicine, Kobe University School of Medicine, Japan. adachi@med.kobe-u.ac.jp
Tomita
M
M
Yamakawa
S
S
Asano
M
M
Naito
T
T
Ueno
Y
Y
D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000032:analysis*; D002853:Chromatography, Liquid; D005260:Female; D007668:Kidney / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D013058:Mass Spectrometry; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; C041011:cholesterol 7-hydroperoxide; D002784:Cholesterol; D010269:Paraquat