Age dependent different influence of carbon tetrachloride on biotransformation of xenobiotics, glutathione content, lipid peroxidation and histopathology of rat liver.
15- and 60-day-old male rats were treated with different doses of CCl4 orally. 24 h later cytochrome P-450 (P450) concentration, 7-ethoxyresorufin O-deethylation (EROD) and 7-pentoxy-resorufin O-deethylation (PEROD) activities were determined. Whereas P450 and EROD are lowered to the same extent in both ages, PEROD shows a more pronounced inhibition in the livers of younger rats. The formation of endogenous lipid peroxides (measured as thiobarbituric acid reactive substances) is drastically increased only in the livers of young rats. The hepatic glutathione (GSH) content was unaffected by CCl4 treatment whereas oxidized glutathione is more increased in the livers of adult rats. This can be caused by a higher activity of GSH-peroxidase in the livers of adult rats. The changes in NADPH-induced lipid peroxidation and chemiluminescence correlate partially with the changes in P450 and biotransformation reactions. Histopathologically the liver damage is more extensive in suckling rats. The necrosis is localized predominantly in the perivenous tissue, which has normally the highest activities of toxification and detoxification enzymes.
Jahn
F
F
Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany.
Reuter
A
A
Karge
E
E
Danz
M
M
Klinger
W
W
D000367:Age Factors; D000818:Animals; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000493:pharmacokinetics*
D008054:Lipid Peroxides; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D005978:Glutathione