Lacidipine protects against cyclosporine-induced nephrotoxicity in rats.
The effect of lacidipine (LA), a new calcium channel blocker with an antioxidant effect, has been studied on cyclosporine (CsA)-induced nephrotoxicity in male Wistar rats. Lacidipine (1 mg/kg BW) was administered orally 3 days before and 14 days concurrently with CsA (50 mg/kg BW orally). Urine volume, Na+, K+, Li+ and creatinine in urine, and blood urea, serum creatinine, lithium, plasma malondialdehyde (MDA) and CsA levels were estimated in blood after 14 days CsA treatment. Kidneys were examined using histological techniques. Blood urea and serum creatinine were increased by 305 and 211%, respectively, with CsA when compared to the saline-treated animals. Creatinine clearance (Ccr) and lithium clearance (Licr) were decreased and proximal tubule fractional reabsorption 1-(Licr/Ccr) was significantly increased with CsA. Lacidipine protected rats from CsA-induced nephrotoxicity. Changes in blood urea, serum creatinine, Ccr, Licr and proximal tubule fractional reabsorption induced by CsA were significantly prevented by LA. There was a 160% rise in MDA levels with CsA, which was significantly reduced equal to control with LA. Histomorphology showed microcalcification with CsA, while it was normal with LA. In rats treated with LA, CsA did not show any microcalcification. Our data suggest that supplementation of LA may be helpful to reduce CsA nephrotoxicity.
Naidu
M U
MU
Central Research Laboratory, Department of Clinical Pharmacology and Therapeutics, Punjagutta, Hyderabad, India.
Kumar
K V
KV
Shifow
A A
AA
Prayag
A
A
Ratnakar
K S
KS
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004095:Dihydropyridines / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007166:Immunosuppressive Agents; C060285:lacidipine; D016572:Cyclosporine; D008094:Lithium