Diazoxide protects against hydrogen peroxide-induced toxicity in the osteoblastic MC3T3-E1 cells

作者：Choi Eun Mi; Kim Gun Hee; Lee Yong Soo^*

来源：European Journal of Pharmacology, 2009, 624(1-3): 45-50.

DOI：10.1016/j.ejphar.2009.09.041

• Diazoxide
• Oxidative stress
• Osteoblast

Treatment of various types of cells with the mitochondrial ATP-sensitive K( ) channel (mK(ATP)) opener has been shown to precondition cells to subsequent injuries and inhibit apoptosis. We exposed cultured osteoblastic MC3T3-E1 cells to hydrogen peroxide (H(2)O(2)) with or without pretreatment with a mK(ATP) opener, diazoxide. A marked decrease in osteoblast viability was evident after 48 h exposure of 0.3 mM H(2)O(2), compared with vehicle-treated cells. Diazoxide (0.001 similar to 10 mu M) treatment significantly (P<0.05) reversed the cytotoxic effect of H(2)O(2) and this effect was blocked by a specific mK(ATP) blocker, glibenclamide. Pretreatment with diazoxide (0.01 similar to 1 mu M) also decreased the release of reactive oxygen species and the increase in oxidative damage markers (protein carbonyl and malondialdehyde) induced by H(2)O(2) in osteoblastic MC3T3-E1 cells. Moreover, H(2)O(2)-induced reduction of differentiation markers, such as alkaline phosphatase, collagen content and calcium deposition was significantly recovered in the presence of diazoxide. In addition, diazoxide (0.01 similar to 1 mu M) decreased the H(2)O(2)-induced production of osteoclast differentiation-inducing factors, such as interleukin (IL)-6 and the receptor activator of nuclear factor-kB ligand (RANKL). These results suggest that diazoxide may be useful for the protection of H(2)O(2)-induced oxidative damage and dysfunction in osteoblastic cells.

• 出版日期2009-12-10