Effect of L-histidinol on cisplatin nephrotoxicity in the rat.
The effect of L-histidinol (LHL) on the acute nephrotoxicity produced by cisplatin (CDDP; 6 mg/kg, i.v.) was investigated in the rat. Intraperitoneal administration of LHL (100 mg/kg x 5 doses, 2 h apart) starting 2 h prior to CDDP single injection produced significant protection of renal function. The attenuation of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations, decreased polyuria, reduction in body weight loss, marked reduction in urinary fractional sodium excretion and glutathione-S-transferase (GST) activity, and increased urine/serum creatinine ratio as well as increased creatinine clearance. LHL significantly ameliorated the toxic renal biochemical changes induced by CDDP. Renal lipid peroxides, glutathione levels and GST activity showed a marked tendency towards the normal values. Accumulation of platinum in renal tissues was significantly decreased in the presence of LHL. It is concluded that LHL can act as a nephroprotectant, and it is suggested that it would have beneficial effects on the kidney in clinical settings.
Badary
O A
OA
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Nagi
M N
MN
Al-Sawaf
H A
HA
Al-Harbi
M
M
Al-Bekairi
A M
AM
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000097:blood; D006400:Hematocrit; D006641:Histidinol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D014508:Urea / Q000097:blood
D000970:Antineoplastic Agents; D006641:Histidinol; D014508:Urea; D012964:Sodium; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin; D011188:Potassium