[Studies on nephrotoxicity of cyclosporin. 1. Nephrotoxicity in rats receiving cyclosporin].
Cyclosporin (CS) is a potent immunosuppressant that has been used in organ transplantation, but it has a serious nephrotoxic effect. To investigate its effects on renal function and structure, we carried out biochemical and morphological examinations in rats. Male Wistar rats each weighing 250 g were used. Rats were given various dose regimens (100, 50, 25 and 10 mg/kg/day) of CS orally over a 21-day period. All the rats were killed and examined on the 22nd day. Blood urea nitrogen (BUN), serum and urinary creatinine and urinary N-acetyl-s-D-glucosaminidase (NAG) were measured before administration and on the 7th, 14th and 21st day after administration. Kidneys were examined with light and electron microscopes. All rats that had received 100 mg/kg/day CS died within 12 days after a severe loss in body weight. Rats that had received 50 or 25 mg/kg/day CS had lost weight which never returned to the weight before administration. A high CS dose caused a significant elevation of BUN unaccompanied by a corresponding rise in serum creatinine. Reduction of creatinine clearance was not prominent during the experimental course. Although the urinary NAG activity was increased in high dose groups, the elevation was not related to dose. Morphological alterations were confined to the proximal tubuli and they consisted of tubular cell vacuolation and increased number of lysosomes. However, these alterations were mild and not related to the CS dose.
Pak
K
K
Department of Urology, Shiga University of Medical Science.
Tomoyoshi
T
T
Nomura
Y
Y
Okabe
T
T
D000118:Acetylglucosaminidase / Q000652:urine; D000284:Administration, Oral; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D003404:Creatinine; D000118:Acetylglucosaminidase