title: Protective effects of alpha lipoic acid versus N-acetylcysteine on ifosfamide-induced nephrotoxicity.
abstract: Ifosfamide (IFO) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors. However, its use is limited due to its serious side effect on kidneys. The side-chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect. Therefore, this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO-induced nephrotoxicity, including free radical generation and the possible role of alpha lipoic acid (ALA) versus N-acetylcysteine (NAC) in protection against this toxicity. Male albino rats were injected intraperitoneally with saline, IFO (50 mg/kg daily for 5 days), IFO + ALA (100 mg/kg daily for 8 days) and IFO + NAC (200 mg/kg daily for 8 days). Kidney malondialdehyde, nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined. Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO. NAC was more nephroprotective than ALA. This study suggests that oxidative stress is possibly involved in the IFO-induced nephrotoxicity in rats. The study also suggests the potential therapeutic role for ALA and NAC against IFO-induced nephrotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tanta, Tanta, Egypt.
authors.forename: Alaa El-Din E
authors.initials: Ael-D
authors.lastname: El-Sisi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tanta, Tanta, Egypt.
authors.forename: Magda E
authors.initials: ME
authors.lastname: El-Syaad
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tanta, Tanta, Egypt.
authors.forename: Karima I
authors.initials: KI
authors.lastname: El-Desoky
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tanta, Tanta, Egypt ethar-moussa@hotmail.com.
authors.forename: Ethar A
authors.initials: EA
authors.lastname: Moussa
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D005978:Glutathione / Q000097:blood; D007069:Ifosfamide / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; D008063:Thioctic Acid; D005978:Glutathione; D007069:Ifosfamide; D000111:Acetylcysteine
keywords: Alpha lipoic acid; N-acetylcysteine; glutathione; histological changes; ifosfamide; lipid peroxidation; nephrotoxicity