title: Downregulation of oxidative and nitrosative apoptotic signaling by L-carnitine in Ifosfamide-induced Fanconi syndrome rat model.
abstract: It is well documented that ifosfamide (IFO) therapy is associated with sever nephropathy in the form of Fanconi syndrome. Although oxidative stress has been reported as a major player in IFO-induced Fanconi syndrome, no mechanism for this effect has been ascertained. Therefore, this study has been initiated to investigate, on gene expression level, the mechanism of IFO-induce nephrotoxicity and those whereby carnitine supplementation attenuates this serious side effect of IFO. To achieve the ultimate goals of this study, adult male rats were assigned to one of four treatment groups, namely, control, L-carnitine, IFO, and IFO plus L-carnitine. Administration of IFO for 5 days significantly increased serum creatinine, blood urea nitrogen (BUN), and total nitrate/nitrite (NOx) production in kidney tissues. In addition, IFO significantly increased mRNA expression of inducible nitric oxide synthase (iNOS), caspase-9, and caspase-3 and significantly decreased expression of glutathione peroxides (GPx), catalase (CAT), and Bcl2 in kidney tissues. Administration of L-carnitine to IFO-treated rats resulted in a complete reversal of the all biochemical and gene expression changes, induced by IFO, to the control values. Data from this study suggest that L-carnitine prevents the development of IFO-induced nephrotoxicity via downregulation of oxidative and nitrosative apoptotic signaling in kidney tissues.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Hafez
authors.forename: Meshan Lafi
authors.initials: ML
authors.lastname: Aldelemy
authors.forename: Abdulaziz M
authors.initials: AM
authors.lastname: Aleisa
authors.forename: Salem S
authors.initials: SS
authors.lastname: Al-Rejaie
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Al-Hosaini
authors.forename: Naif O
authors.initials: NO
authors.lastname: Al-Harbi
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Al-Harbi
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Shabanah
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D002331:Carnitine / Q000494:pharmacology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005198:Fanconi Syndrome / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007069:Ifosfamide / Q000737:chemistry; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D015538:Nitrosation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009566:Nitrates; D009573:Nitrites; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D020169:Caspases; D002331:Carnitine; D007069:Ifosfamide