title: Abrogation of cisplatin-induced nephrotoxicity by emodin in rats.
abstract: Nephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen species in renal cortex, and emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions. Therefore, we tested here the possible ameliorative effect of emodin on CP nephrotoxicity in rats. Emodin was given orally (10 mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Five days after CP treatment, rats were killed, and blood and urine samples, and kidneys were collected for the assessment of histopathological renal damage and apoptosis, and for biochemical estimation of creatinine and urea concentrations in plasma and urine, several cytosolic antioxidant enzyme activities in kidneys, and urinalyses. CP significantly increased the concentrations of urea and creatinine, and decreased creatinine clearance. It also significantly reduced cortical glutathione concentration and the activity of superoxide dismutase. CP treatment significantly increased urine volume and N-acetyl-β-D-glucosaminidase activity and significantly decreased osmolarity and protein concentrations. Emodin treatment markedly and significantly mitigated all these effects. Sections from saline- and emodin-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with emodin. The concentration of CP in the cortical tissues was not significantly altered by emodin treatment. The results suggested that emodin had ameliorated CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies emodin may be considered a potentially useful nephroprotective agent.
authors: Department of Pharmacology, College of Medicine and Health Sciences, Sultan Qaboos University, P. O. Box 35, Al Khod, Oman.
authors: Badreldin H
authors: BH
authors: Ali
authors: Suhail
authors: S
authors: Al-Salam
authors: Isehaq S
authors: IS
authors: Al Husseini
authors: Intisar
authors: I
authors: Al-Lawati
authors: Mostafa
authors: M
authors: Waly
authors: Javed
authors: J
authors: Yasin
authors: Mohamed
authors: M
authors: Fahim
authors: Abderrahim
authors: A
authors: Nemmar
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D004642:Emodin / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000473:pathology; D009994:Osmolar Concentration; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014508:Urea / Q000378:metabolism
chemical_list: D014508:Urea; D003404:Creatinine; D013482:Superoxide Dismutase; D000118:Acetylglucosaminidase; D005978:Glutathione; D004642:Emodin; D002945:Cisplatin