Effect of the spin-labelled 1-ethyl-1-nitrosourea on CCNU-induced oxidative liver injury.
This study was carried out to determine the effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-l-nitrosourea (SLENU), recently synthesised in our laboratory, and vitamin E as positive control on 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) - free radical induced oxidative injuries in the liver of mice. Specifically, alterations in malonyl dialdehyde (MDA) level and activities of some antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured in liver homogenates from tumour-bearing C57 black mice after treatment with solutions of CCNU (30 mg/kg) and SLENU (100 mg/kg), both administered intraperitoneally. CCNU-induced increase in MDA level, SOD and CAT activities were suppressed by SLENU. The present results and those from a previous report demonstrated superoxide scavenging activities (SSA) of the nitrosourea SLENU and enabled us explain the protective effect of the spin-labelled nitrosourea on CCNU-induced oxidative stress in the liver of mice. This protective effect is through the scavenging of *O2- and by an increased production of *NO. Thus, a potential for developing new combination chemotherapy in cancer is seen.
Gadjeva
V
V
Department of Chemistry and Biochemistry, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria. vgadjeva@mf.uni-sz.bg
Tolekova
A
A
Vasileva
M
M
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000517:prevention & control*; D005038:Ethylnitrosourea / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008130:Lomustine / Q000031:analogs & derivatives* / Q000633:toxicity*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D013113:Spin Labels; D014810:Vitamin E; D009569:Nitric Oxide; D008130:Lomustine; D002374:Catalase; D013482:Superoxide Dismutase; D005038:Ethylnitrosourea