The effects of topotecan on lipid peroxidation and antioxidant enzyme levels in rabbit liver tissue.
BACKGROUND
To evaluate the possible influence of topotecan therapy on lipid peroxidation and antioxidant enzymes in rabbit liver tissue, the levels of thiobarbituric acid reactive substances (TBARS) and activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were investigated.


METHODS
A total of 24 adult, healthy New Zealand rabbits were divided into three groups (n = 8). Topotecan was administered intravenously via the ear vein for 3 days at 0.25 mg/kg/day for the low-dose group and 0.50 mg/kg/day for the high-dose group; physiological saline was used for the control group. All animals were sacrificed on day 15. Livers were removed and homogenised. The homogenate supernatant was used for measurement of TBARS levels, and SOD, GSH-Px, and CAT enzyme activities (expressed as IU/mg protein).


RESULTS
There were significant differences in the TBARS level and GSH-Px activity between control and the topotecan treatment groups. TBARS level of topotecan treatment groups was higher than control (89% and 126%, respectively, P = 0.001). It was also significantly higher in the high-dose group than the low-dose group (20%; P = 0.011). GSH-Px activity was lower in the low- and high-dose topotecan groups than the control (42% [P = 0.002] and 65% [P = 0.001], respectively). Enzyme activity was lowest in the high-dose group and the difference was also significant when compared with the topotecan groups (40%; P = 0.001). Although there was some decrease in SOD and CAT activities in the topotecan-treated groups, differences from the control group were not significant.


CONCLUSIONS
These findings suggest that topotecan treatment results in an increase in lipid peroxidation and a decrease in antioxidant enzyme activities in healthy liver tissue from rabbits. We believe that the addition of antioxidants to topotecan therapy may reduce the harmful effects of topotecan on liver tissue.
Kisa
Ucler
U
Department of Biochemistry and Clinical Biochemistry, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey. uclerkisa@kku.edu.tr
Caglayan
Osman
O
Kacmaz
Murat
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004338:Drug Combinations; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D019772:Topotecan / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000975:Antioxidants; D004338:Drug Combinations; D017392:Thiobarbituric Acid Reactive Substances; D019772:Topotecan; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase