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KMID : 0350519920450020699
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Journal of Catholic Medical College
1992 Volume.45 No. 2 p.699 ~ p.713
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Protective Effect of Calcium Channel Blocker against Contrast Media Induced Nephrotoxicity in Normal and Uremic Rats
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Abstract
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Radiopaque contrast media(CM) are well known to cause nepthrotoxicity in varying degrees. Its major mechanisms are thought to be due to changes of the renal hemodynamics and direct toxicity to the renal proximal tubule. Extracellular calcium
plays
a
part in the process of CM-induced nephrotoxicity and calcium channel blockers have the positive effects on the renal hemodynamics and cytoprotective effect.
This study was undertaken to evaluate any difference in the degree of nephrotoxicity between ionic and nonionic CM, and to examine the protective effect of verapamil ans a calcium channel blocker for the CM-induced nephrotoxicity of normal and
uremic
rats. One hundred and twenty Sprague-Dawley rats, weighing 185-250 g were divided into two groups; normal(N) and glycerol induced uremic(U), each consisting sixty rats. Each group was subdivided into 6 with 10 rats in each subgroups. Subgroup
1(N1,
U1)
was given saline and served as a control. Subgroup 2(N2, U2) was given diatrizoate, whereas subgroup 3(N3, U3) was given iopromide. Subgroup 4, 5 and 6 were given verapamil, along with eigher saline, diatrizoate or iopromide. Blood and 24 hours
were
collected on the 1st day and 3rd day after indusion and then right kidney was removed for light microscopic observation. In addition creatinine(Cr) and urea of serum and, creatinine, total protein, onzymes, such as alkaline phosphatase(ALP),
gammaglutamyl transferase(GGT), N-acetyl-βglucosaminidase(NAG) and lactate dehydrogenase(LDH) of 24 urine were measured. Also creatinine clearance(Ccr) was calculated.
@ES The results were as follows:
@EN 1. On the 3rd day, serum urea was more significantly increased in N2 group than in N1 group(P=0.021) and serum creatinine of U5 group was markedly decreased compared with that of U2 group(P=0.015).
2. The lst day Ccr of N2 group was markedly diminished compared with that of N1 group(P=0.012), but increased in N5 group(P=0.015), compared with that of N2 group.
3. There was no definite difference of total urine protein between groups. The 1st day ALP(P=0.001), GGT(P=0.014), LDH(P=0.02) of N2 group were significantly elevated compared with tose of N1 group. Also the 1st day ALP(P=0.019) and LDH(P=0.044)
of N3
group showed a definite increase over N1 group. The 1st day ALP(P=0.028), and LDH(P=0.014) of N5 group were markedly reduced compared with those of N2 group and the 1st day LDH(P=0.011) of N6 group was also diminished when compared with that of
N3
group. The 1st day ALP(P=0.002), GGT(P=0.037) and the 3rd day ALP(P=0.045) of U2 group were significantly incresed compared with those of U1 group. However, decreased values of the 1st day ALP(P=0.002), 3rd day NAG(P=0.04) and LDH(P=0.019) of U5
group
were noted when compard to those of U2 group.
4. The light microscopic examination of uremic and CM infused normal rats revealed some degree of vacuolization and/or necrosis of renal proximal tubular epithelial cell. The changes were severe in the uremic rats, however, no definite
difference
was
found between the experimental subgroups.
In conclusion, ionic CM was more nephrotoxic than nonionic CM. The CM-induced nephrotoxicity was transient for almost every cases. The protective effect of calcium channel blocker against CM induced nephrotoxicity was noted in both normal and
uremic
rats, but was limited in the case of uremic rats.
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KEYWORD
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