title: Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: role of oxidative stress and caspase-3.
abstract: Cadmium (Cd) is an environmental and industrial pollutant that can induce a broad spectrum of toxicological effects that affect various organs in humans and experimental animals. This study aims to investigate the effect of betaine supplementation on cadmium-induced oxidative impairment in rat kidney. The animals were divided into four groups (n=10 per group): control, cadmium, betaine and betaine+cadmium (1) saline control group; (2) cadmium group in which cadmium chloride (CdCl2) was given orally at a daily dose of 5 mg/kg body weight for four weeks; (3) betaine group, in which betaine was given to rats at a dose of 250 mg/kg/day, orally via gavage for six weeks; (4) cadmium+betaine group in which betaine was given at a dose of 250 mg/kg/day, orally via gavage for two weeks prior to cadmium administration and concurrently during cadmium administration for four weeks. Cadmium nephrotoxicity was indicated by elevated blood urea nitrogen (BUN) and serum creatinine levels. Kidneys from cadmium-treated rats showed an increase in lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) concentration and reductions in total antioxidant status (TAS), reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase concentration (SOD) and catalase activity. Caspase-3 activity, a marker of DNA damage was also elevated in renal tissues of cadmium-treated rats. Pre-treatment of rats with betaine substantially attenuated the increase in BUN and serum creatinine levels. Betaine also inhibited the increase in TBARS concentration and reversed the cadmium-induced depletion in total antioxidant status, GSH, GSH-Px, SOD and catalase concentrations in renal tissues. Renal caspase-3 activity was also reduced with betaine supplementation. These data emphasize the importance of oxidative stress and caspase signaling cascade in cadmium nephrotoxicity and suggest that betaine pretreatment reduces severity of cadmium nephrotoxicity probably via antioxidant action and suppression of apoptosis.
authors.affiliation: Department of physiology and Pharmacology, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. Electronic address: hananhhagar@yahoo.com.
authors.forename: Hanan
authors.initials: H
authors.lastname: Hagar
authors.affiliation: Department of Pharmacology, College of Pharmacy Umm Al-Qura University, Makkah, Saudi Arabia.
authors.forename: Waleed
authors.initials: W
authors.lastname: Al Malki
mesh_terms: D000818:Animals; D001622:Betaine / Q000494:pharmacology / Q000627:therapeutic use*; D002104:Cadmium / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000188:drug therapy / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D002104:Cadmium; D001622:Betaine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione
keywords: Betaine; Cadmium; Caspase-3; Lipid peroxidation; Nephrotoxicity; Oxidative stress