The effect of calcium channel blockers on cyclosporine A (Cs A) induced nephrotoxicity in rats.
The limiting factor in the therapeutical use of cyclosporine A (Cs A) is its nephrotoxicity, which may lead to renal failure. Cs A nephrotoxicity may present itself as an acute decrease in GFR, or as a chronic renal injury. Nephrotoxicity is caused by the indirect vasoconstriction effect mainly on proximal tubule and afferent arteriols. In our study we have concentrated on the effect of Ca-channel blockers on Cs A nephrotoxicity. As parameters of toxic kidney damage we have used the urine levels of the following enzymes: N-acetyl-beta-D-glucosaminidase (NAG), gama-glutamyltransferase (GMT) and alkaline phosphatase (ALP). Daily intragastric application of verapamil (V) (dose 1.0 mg/kg BW) or nifedipine (N) (dose 0.1 mg/kg BW) was started in a group of male Wistar rats. Cs A (Sandimun Sandoz, Switzerland) was applied daily intraperitoneally 30 minutes after the application of V or N. The dose of Cs A ranged from 5 mg/kg BW to 25 mg/kg BW in individual groups. The animals were observed for 10 days after the drugs application. Urine samples were collected and examined at the end of the whole experiment. The individual parameters were evaluated in the groups receiving the 3 different doses of Cs A (5-25 mg/kg BW). The serum creatinine rose moderately during the experiment. When the Ca-channel blockers were administered, the rise was not as steep, but when the highest dose of Cs A was administered, the Ca-channel blockers did not influence the elevation of the serum creatinine. Using the standard dose of Cs A (5 mg/kg BW) the protective effect of Ca-channel blockers can be found. In higher doses of Cs A this protective effect was not expressed.
Zima
T
T
First Department of Medical Chemistry and Biochemistry, 1st Medical Faculty Charles University, Prague, Czech Republic.
Nĕmecek
K
K
Hátle
K
K
Bártová
V
V
Stípek
S
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016572:Cyclosporine; D003404:Creatinine; D014700:Verapamil; D009543:Nifedipine