Protective Effects Of Kakkalide On Ethanol-Induced DNA Damage On Various Tissues And Organs In Mice

Flos Puerariae is a traditional Chinese medicine, which has been clinical used to counteract symptoms associated with alcohol drinking. Pharmacological studies have shown that Kakkalide, an isoflavones of Flos Puerariae, have the role of antioxidant, anti-high blood cholesterol, anti-inflammatory and anti-inebriation.Ethanol abuse is one of the most costly health problems in the world. The genotoxicity of ethanol has been widely concerned in the recent years. Ethanol-induced oxidative DNA damage leads to a variety of diseases and potential neurotoxicity and carcinogenety. Our previous studies have indicated that acute and long-term ethanol administration can lead to oxidative DNA damage of peripheral blood cells and cells in different brain regions. Meanwhile,8-OHdG in urine, an oxidative product of DNA was increased.In present study, we investigated the effect of anti-inebriation hangover of Kakkalide and the protective effects of Kakkalide on ethanol-induced DNA damage on various tissues and organs in mice as well as the possible mechanisms involved.Firstly, Kakkalide shortened ethanol-induced sleep time (loss of righting reflex) in mice that were given ethanol intraperitoneally.Meanwhile, the effects of Kakkalide on DNA in mice peripheral leukocytes, cerebellum, hippocampus and liver cells were detected by alkaline single cell gel electrophoresis. The results showed that Kakkalide administration could not induce DNA damage in mice peripheral leukocytes, cerebellum, hippocampus and liver cells, however, Kakkalide markedly decreased the levels of DNA single-strand breaks induced by ethanol.In order to reveal the possible protective mechanisms of Kakkalide on DNA single-strand breaks, the effect of Kakkalide on ethanol-induced urinary 8-OHdG, an oxidative product of DNA, was measured by using HPLC-ECD. The results showed that Kakkalide 400 mg/kg administration for 1 d,3 d and 7 d inhibited the increase of urinary 8-OHdG excretions induced by ethanol. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in peripheral leukocytes, cerebellum, hippocampus brain tissue and liver cells in mice with acute alcoholism were also detected. The results indicated that Kakkalide could reverse the activity of SOD and the content of MDA in mice peripheral leukocytes, cerebellum, hippocampus and liver cells with acute ethanol administration.In conclusion, intake of Kakkalide could protect ethanol-induced genotoxicity on various tissues and organs in mice and the mechanisms could be associated with antioxidation. Kakkalide could be used in the prevention and treatment of problems associated with ailments induced by alcohol abuse.