Effect of verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver

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Abstract
The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37°C and 6 days at 4°C were 80.3±5.2 and 31.6±2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0±3.9% (PM of verapamil, 21.2±5.8% (PPM of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 μM of verapamil followed by incubation for 6 h at 37°C. In the livers that were flushed and stored at a warm temperature for 6h, verapamil reduced the increase of tissue lipid peroxidation product (P<0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is though that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.