[Studies on nephrotoxicity of cyclosporin. II. Nephrotoxicity in rats receiving cyclosporin and sulfamethoxazole-trimethoprim].
A cyclosporin (CS) has a serious nephrotoxic effect which is synergistic with sulfamethoxazole-trimethoprim (ST) on renal allograft recipients. The effects of CS and ST on renal function and structure, were examined biochemically and morphologically in rats. Male Wistar rats each weighing 250 g were given various dose regimens (CS 50 mg/kg + ST 600 mg/kg, CS 25 mg/kg + ST 600 mg/kg, CS 10 mg/kg + ST 600 mg/kg) orally for 21 days, and 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. The serum levels of CS, sulfamethoxazole (SMX) and trimethoprim (TMP) were measured on the 21st day after administration. Kidneys were examined by light and electron microscopy. All rats that had received 50 mg/kg CS and 600 mg/kg ST died within 9 days after a severe loss in body weight. Rats that had received 25 mg/kg CS and 600 mg/kg ST had lost weight. A high dose CS and ST caused a significant elevation of BUN. The level of serum creatinine was significantly elevated only in rats that had received 25 mg/kg CS and 600 mg/kg ST. Decrease in creatinine clearance was not significant and the urinary NAG activity was not altered significantly during the experimental course. Morphological alterations were confined to the proximal tubuli and they consisted of PAS positive globules, loss of nuclei, tubular cell vacuolation and increased number of lysosomes. However, these alterations were mild and not related to the dose of CS and ST.(ABSTRACT TRUNCATED AT 250 WORDS)
Pak
K
K
Department of Urology, Shiga University of Medical Science.
Tomoyoshi
T
T
Nomura
Y
Y
Okabe
H
H
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000652:urine; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D004338:Drug Combinations / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D004357:Drug Synergism; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D014295:Trimethoprim / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
D003524:Cyclosporins; D004338:Drug Combinations; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D003404:Creatinine; D013420:Sulfamethoxazole