DNA damage and the effect of antioxidants in streptozotocin-treated mice.
Streptozotocin (STZ) has drawn attention as a potential source of oxidative stress, which induces genotoxicity. We investigated the effects of STZ on DNA damage in the liver and kidney, as well as the protective effects of antioxidants, by using the alkaline single-cell gel electrophoresis assay, and by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (8-OHdG) to dG. A single intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and also caused DNA damage in the liver and kidney, which recovered slowly with time. Antioxidants,(ascorbic acid, trolox and probucol) prevented the STZ-induced elevation of DNA damage in the liver and kidney and inhibited the increase in serum levels of AST, ALT and BUN. Thus ascorbic acid, trolox, and probucol protected the mice against STZ-induced DNA damage that might contribute to the development of hepatic or renal disease.
Imaeda
A
A
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd, 3-16-89 Kashima, Yodogawa-ku, Osaka 532-8505, Japan. a-ima@tanabe.co.jp
Kaneko
T
T
Aoki
T
T
Kondo
Y
Y
Nagase
H
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D013311:Streptozocin / Q000633:toxicity*
D000975:Antioxidants; D013311:Streptozocin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine