For several decades there has been an active search for pharmacological agents that could render the tissue more tolerant to ischemia. In recent years, cardioprotective effects of adenosine and K+ channel openers have been established by various investigators. However, little information is available about the action of these agents in epithelial cells. This study was undertaken to determine whether these agents might have protective effect against oxidant-induced injury in renal epithelial cells. Opossum kidney (OK) cells and H2O2 were employed as an experimental cell and injury model for the present study. Adenosine protected cells effectively against H2O2-induced injury determined by trypan blue exclusion ability, LDH release, and MTT reduction assay. The effect of adenosine was concentration-dependent upto 5x10-3 M. The protective effect of adenosine was mimicked by N6-cyclopentyladenosine (CPA), a selective A1 receptor agonist, whereas blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX) suggesting that the protection mechanism is mediated by A1 receptors. The sensitivity to pertussis toxin of the adenosine-induced protection against H2O2-induced cell death was consistent with the hypothesis that the A1 receptor mediates the protection mechanism via the Gi protein. K+ channel openers such as diazoxide and pinacidil were also effective to prevent H2O2-induced cell death. In addition, the protection against cell death by adenosine as well as the K+ channel openers was blocked significantly by 5-hydroxydecanoate or glibenclamide, suggesting that opening of ATP-sensitive K+ channels is implicated in the protection mechanism. Adenosine or potassium channel openers did not affect the activities of catalase, superoxide dismutase, and glutathione peroxidase in these cells. In conclusion, the present study provides evidence for the action of adenosine and potassium channel openers as effective cytoprotectants against ROS-mediated cell injury in renal epithelial cells.
Source: Korean Journal of Physiology & Pharmacology.2000 Oct;4(Suppl):S18-S18
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