Protective Effect of Combined Allopurinol and Verapamil Given at Reperfusion in Severe Renal Ischemia

Abstract

This study investigates the role of verapamil, a calcium channel blocker, combined with allopurinol, a xanthine-oxidase inhibitor, when given at reperfusion afer severe renal ischemia injury in the rat. Male Sprague-Dawley rats were subjected to 60 minutes of warm ischemia by cross clamping the whole left renal pedicle (artery and vein). At the end of ischemia, the clamps were removed and a contralateral nephrectomy was performed. The animals (n = 40 per group) were divided into five groups: Group 1, ischemic control (IC) receiving lactated Ringer's; Group 2, allopurinol (A) 100 mg/kg; Group 3, verapamil (V) 1.25 mg/kg; Group 4, receiving a combination of A + V at the same concentrations; and Group 5, sham group. Each drug was given intravenously at the end of the ischemic period at reperfusion. Survival was evaluated at 7 days. Renal damage was assessed by kidney function tests (serum creatinine and blood urea nitrogen, or BUN), light histology. Lipid peroxidation was measured in renal tissue using the TBA (thiobarbituric acid) assay. The best survival rate was seen in the combination group of A + V (70% at 7 days; p >. 01 vs. control). Single drugs were not as effective as the combination when compared to the IC. Serum creatinine at 24 and 48 hours showed a significant difference between the IC and treatment groups. At 72 hours there were no differences among the treated groups. Histological damage was more pronounced in the IC (Grade 4.0) than in the allopurinol (3.4 ± 0.8), verapamil (3.0), or A + V (2.2 ± 0.04). It was evident that the combination of A + V had the most significant beneficial effect in the survival and histological structure.

Key Words:

• allopurinol
• verapamil
• renal ischemia