Acute cyclosporin A renal dysfunction in dogs reversed by calcium antagonists and antiplatelet agents.
The aim of this study was to assess the effect of nifedipine and piracetam alone or in combination in the protection of renal function and morphology after cyclosporin A (CyA) administration. Thirty healthy mongrel dogs with a mean body weight of 15 kg were sacrificed. Six animals (group C) were given CyA 20 mg/kg body weight per os, while the remaining groups (8 animals each) were given concomitantly 20 mg nifedipine (group CN) or 4 g of piracetam (group CP), or both drugs in combination (group CNP). After 5 days of drug administration the animals were anesthetized, both kidneys were exposed, and functional tests were performed. Then the kidneys were removed for histological study. The mean plasma CyA levels in the four groups were 1765 +/- 685 ng/mL, 1300 +/- 324 ng/mL, 1116 +/- 491 ng/mL and 1600 +/- 290 ng/mL, respectively. Urine volume, creatinine, urea, and osmolar clearances were significantly higher in the groups CN, CP, and CNP compared to the control group C (p < 0.01). Urine sodium concentration was significantly higher (p < 0.05 or p < 0.01) in nifedipine groups than in the other two groups of animals, while the fractional excretion of sodium (FENa%) was significantly higher (p < 0.01) in all treated groups compared to controls. Plasma thromboxane-B2 levels were significantly reduced by each drug alone or in combination (p < 0.01). Morphological lesions, similar in all groups, did not correlate with the functional improvement.(ABSTRACT TRUNCATED AT 250 WORDS)
Grekas
D
D
First Medical Department, University Hospital AHEPA, Thessaloniki, Greece.
Alivanis
P
P
Kalekou
H
H
Papayianni
K
K
Karamouzis
M
M
Tourkantonis
A
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016572:Cyclosporine / Q000097:blood / Q000633:toxicity*; D004285:Dogs; D004347:Drug Interactions; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D010889:Piracetam / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D013928:Thromboxane A2; D016572:Cyclosporine; D009543:Nifedipine; D010889:Piracetam