Effect of CPT-11 on lipid peroxide level in mouse tissues.
We examined the effects of CPT-11 on lipid peroxide level and glutathione peroxidase (GSHpx) activity as indices of the toxicity of this antitumor agent in mouse and rat tissues. After CPT-11 (100 mg/kg, i.p.) administration, the lipid peroxide level in the heart increased 1.5 fold (mice) and 1.3 fold (rats) over the control levels. GSHpx activity decreased to 64% of the control. In the lung, the lipid peroxide level and GSHpx activity increased 2.5 fold and decreased to 74% after CPT-11 administration, respectively, compared with the control values. These results suggested that CPT-11 may cause cardiotoxicity and pulmotoxicity. In rat bone marrow, the lipid peroxide level increased on the 2nd day after CPT-11 injection. We suggest that in both single and combination treatment with CPT-11, the possibility of side effects should be taken into consideration.
Sadzuka
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka.
Hirota
S
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D005979:Glutathione Peroxidase / Q000378:metabolism*; D000077146:Irinotecan; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000972:Antineoplastic Agents, Phytogenic; D008054:Lipid Peroxides; D009249:NADP; D000077146:Irinotecan; D005979:Glutathione Peroxidase; D002166:Camptothecin