Dehydroepiandrosterone pretreatment protects rats against the pro-oxidant and necrogenic effects of carbon tetrachloride.
A single intraperitoneal injection of dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one, DHEA) 17 hr before carbon tetrachloride (CCl4) poisoning protects rats against liver injury induced by the haloalkane. In liver homogenates, both the increase in malondialdehyde production and the formation of fluorescent lipid peroxidation products are significantly reduced. Also, liver microsomes obtained from DHEA-pretreated rats incubated in vitro with CCl4 are less susceptible to lipid peroxidation than microsomes from normal animals. The release of liver enzymes into the blood is much reduced in DHEA-pretreated rats, confirming a cause-effect relationship between lipid peroxidation and hepatocyte death. Treatment with DHEA inhibits neither glucose-6-phosphate dehydrogenase activity in the cytosol, nor the microsomal mixed function oxidase system (cytochrome P450 content, aminopyrine demethylase and ethoxycoumarin de-ethylase activities). In animals treated with DHEA, the liver content of total glutathione and vitamin E is not modified. These results support the hypothesis that DHEA protects against CCl4-induced liver injury through its own antioxidant activity, rather than by interfering with the metabolism of the toxin or with the tissue level of primary antioxidants.
Aragno
M
M
General Pathology Institute, Sassari, Italy.
Tamagno
E
E
Boccuzzi
G
G
Brignardello
E
E
Chiarpotto
E
E
Pizzini
A
A
Danni
O
O
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000517:prevention & control*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000032:analysis; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats
D000975:Antioxidants; D003687:Dehydroepiandrosterone; D008315:Malondialdehyde; D002251:Carbon Tetrachloride