The effects of mibefradil, a T-type Ca2+ channels blocker, on the renal dysfunction and injury caused by ischemia-reperfusion of the rat kidney

This study was designed to determine the possible protective effect of mibefradil on renal ischemia/reperfusion (I/R) injury. Unilaterally nephrectomized Sprague-Dawley rats were subjected to 60 min of left renal ischemia followed by 45 min of reperfusion. Group 1 were sham-operated animals; group 2, I/R/untreated animals; and group III, I/R/ mibefradil-treated animals. A 99mTc-DTPA scan was taken to measure kidney perfusion, glomerular filtration rate (GFR) and the time elapsed from isotope injection to the maximum of the curve. Serum creatinine, blood urea nitrogen ( BUN), kidney malondialdehyde (MDA) level were determined as well as examining the kidneys histologically. Treatment of rats with mibefradil produced a significant reduction in the serum levels of creatinine and urea nitrogen. T-max-sec ( renal perfusion) was significantly lower in group 2 than in groups 1 and 3. The GFR was markedly greater in group 3 than in the group 2. The Tmax-min was significantly greater in group 2 than in group 3. Mibefradil treatment significantly decreased the MDA levels. The histopathologic score was significantly less in the group 3 rats compared with group 2 rats. Kidneys of group 2 rats showed tubular cell swelling, cellular vacuolization, pyknotic nuclei, medullary congestion, and moderate to severe necrosis. Treatment with mibefradil preserved the normal morphology of the kidney and shows normal glomeruli and slight edema of the tubular cells. These findings suggest that mibefradil reduces the renal dysfunction associated with I/R of the kidney.