title: Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats.
abstract: Cisplatin is one of the most potent chemotherapeutic antitumor drugs used in the treatment of a wide range of solid tumors. Its primary dose-limiting side effect is nephrotoxicity. This study aims to investigate the effect of betaine supplementation on cisplatin-induced nephrotoxicity. A single intraperitoneal injection of cisplatin (5mg/kg) deteriorated the kidney functions as reflected by elevated blood urea nitrogen and serum creatinine levels. Oxidative/nitrosative stress was evident in cisplatin group by increased renal thiobarbituric acid-reactive substances (TBARS), an indicator of lipid peroxidation, reduced renal total antioxidant status and increased renal nitrite concentration. Cisplatin resulted in a decline in the concentrations of reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase in renal tissues. Renal tumor necrosis factor-α (TNF-α) was also elevated. Expressions of nuclear factor-kappa B (NF-κB) and caspase-3 were up-regulated in renal tissues as indicated by immunohistochemical analysis. Histopathological changes were observed in cisplatin group. Betaine supplementation (250 mg/kg/day) orally via gavage for 21 days prior to cisplatin injection was able to protect against deterioration in kidney function, abrogate the decline in antioxidants enzymes and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, betaine inhibited NF-κB and caspase-3 activation and improved the histological changes induced by cisplatin. Thus, the present study demonstrated the renoprotective nature of betaine by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in kidney tissues of cisplatin treated rats. Betaine could be a beneficial dietary supplement to attenuate cisplatin nephrotoxicity.
authors.affiliation: Pharmacology unit, Physiology Department, College of Medicine and King Khalid University Hospital, King Saud University, Saudi Arabia; Pharmacology& Toxicology Department, Pharmacy College, Zagazig University, Egypt. Electronic address: hananhhagar@yahoo.com.
authors.forename: Hanan
authors.initials: H
authors.lastname: Hagar
authors.affiliation: Pharmacology unit, Physiology Department, College of Medicine and King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Azza El
authors.initials: AE
authors.lastname: Medany
authors.affiliation: Clinical Chemistry Unit, Pathology Department, College of Medicine and King Khalid University Hospital, King Saud University, Saudi Arabia; Biochemistry Department, Medical College, Ain Shams University, Egypt.
authors.forename: Reem
authors.initials: R
authors.lastname: Salam
authors.affiliation: Anatomy Department, College of Medicine and King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Gamila El
authors.initials: GE
authors.lastname: Medany
authors.affiliation: Pharmacology unit, Physiology Department, College of Medicine and King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Omina A
authors.initials: OA
authors.lastname: Nayal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001622:Betaine / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000633:toxicity*; D019587:Dietary Supplements; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D015538:Nitrosation; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D009566:Nitrates; D009573:Nitrites; D001622:Betaine; D002945:Cisplatin
keywords: Acute renal injury; Betaine; Caspase-3; Cisplatin; Nuclear factor-kappa.; Oxidative stress