Toxic effect of concomitant administration of cyclosporin A and acyclovir on renal function and morphology in rats.
The immunosuppressive agent cyclosporin A (CyA) and the antiviral drug acyclovir may cause renal functional impairment. CyA-induced immunosuppression increases the rate of viral infections. Therefore we were interested to determine whether short-term co-administration of CyA and acyclovir involves an increased nephrotoxic risk. Male Wistar rats were treated with CyA (20 mg/kg body wt., s.c., once daily for 8 days), acyclovir (15 mg/kg body wt., s.c., 3-times daily for the last 5 days) or a combination of CyA and acyclovir. Blood levels of CyA were determined after a single dose. Urine was monitored for volume, osmolality, total protein and N-acetyl-beta-D-glucosaminidase (beta-NAG). Concentrations of blood urea nitrogen (BUN) and plasma-creatinine were determined (day 9). Renal cortical slices were monitored for accumulation of weak organic acids (para-aminohippurate, PAH) and bases (tetra-ethylammonium, TEA) and for malondialdehyde (MDA) content. Renal histology was also examined. CyA induced a decrease in body and kidney weight, in urine osmolality and in the excretion of total protein. Plasma-creatinine and BUN as well as MDA content of renal tissues were increased by CyA. Acyclovir alone did not induce significant changes. In comparison to CyA values, urine volume and beta-NAG excretion were enhanced and TEA accumulation depressed by the concomitant administration of CyA and acyclovir. CyA- or acyclovir-treatment alone did not result in significant morphological changes. In the group co-administered CyA/acyclovir, the kidneys showed mild to moderate signs of tubulopathy. Short-term co-administration of CyA and acyclovir was concluded to have possibly increased nephrotoxic potential.
Hannemann
J
J
Department of Internal Medicine II, Medical University of Lübeck, Germany.
Wunderle
W
W
Yousif
T
T
Krüger
S
S
Baumann
K
K
D000118:Acetylglucosaminidase / Q000652:urine; D000212:Acyclovir / Q000633:toxicity*; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000633:toxicity*; D004338:Drug Combinations; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D010130:p-Aminohippuric Acid
D000998:Antiviral Agents; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D000118:Acetylglucosaminidase; D000212:Acyclovir; D010130:p-Aminohippuric Acid