Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats.
The effect of aminoguanidine (AG) on nephrotoxicity induced by cisplatin (CDDP) was investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced nephrotoxicity, manifested biochemically by a significant elevation in serum urea, creatinine and a severe decrease in serum albumin. Moreover, marked increases in kidney weight, urine volume and urinary excretion of albumin were observed. Nephrotoxicity was further confirmed by a significant decrease in glutathione-S-transferase (GST, E.C. 2.5.1.18), glutathione peroxidase (GSH-Px, E.C. 1.11.1.9) and catalase (E.C. 1.11.1.6) and a significant increase in lipid peroxides measured as malondialdhyde (MDA) in kidney homogenates. Administration of AG (100 mg/kg per day p.o.) in drinking water 5 days before and 5 days after CDDP injection produced a significant protection against nephrotoxicity induced by CDDP. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, AG tended to normalize decreased levels of serum albumin. Urine volume, urinary excretions of albumin and GST and kidney weight were significantly decreased. Moreover, AG prevented the rise of MDA and the reduction of GST and GSH-Px activities in the kidney. These results suggest that AG has a protective effect on nephrotoxicity induced by CDDP and it may therefore improve the therapeutic index of CDDP.
Mansour
Mahmoud A
MA
Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. mahmedm@ksu.edu.sa
Mostafa
Adel M
AM
Nagi
Mahmoud N
MN
Khattab
Mahmoud M
MM
Al-Shabanah
Othman A
OA
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D014556:Urine
D000970:Antineoplastic Agents; D006146:Guanidines; D008315:Malondialdehyde; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin; C004479:pimagedine