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.