Abstract

Exposure to higher levels of arsenic is a serious threat affecting human health worldwide. We investigated the protective role of betaine (N,N,N-trimethylglycine) against sodium arsenite-induced renal dysfunction in rats. Sodium arsenite (5 mg/kg, oral) was given to rats for 4 weeks to induce nephrotoxicity. Betaine (125 and 250 mg/kg, oral) was administered in rats for 4 weeks along with sodium-arsenite feeding. Arsenic-induced renal dysfunction was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium, and microproteinuria. Oxidative stress in rat kidneys was determined by assaying thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels. Furthermore, hydroxyproline assay was done to assess renal fibrosis in arsenic intoxicated rats. Hematoxylin-eosin and picrosirius red staining revealed pathological alterations in rat kidneys. Renal endothelial nitric oxide synthase (eNOS) expression was determined by immuno-histochemistry. Concurrent administration of betaine abrogated arsenic-induced renal biochemical and histological changes in rats. Betaine treatment significantly attenuated arsenic-induced decrease in renal eNOS expression. In conclusion, betaine is protective against sodium arsenite-induced renal dysfunction, which may be attributed to its anti-oxidant activity and modulation of renal eNOS expression in rat kidneys.

摘要

暴露于较高水平的砷是影响全世界人类健康的严重威胁。我们研究了甜菜碱（N,N,N-三甲基甘氨酸）对亚砷酸钠诱导的大鼠肾功能障碍的保护作用。给大鼠服用亚砷酸钠（5 mg/kg，口服）4 周以诱导肾毒性。甜菜碱（125 和 250 mg/kg，口服）在大鼠中给药 4 周，同时喂食亚砷酸钠。通过测量血清肌酐、肌酐清除率、尿素、尿酸、钾、钠的排泄分数和微量蛋白尿来证明砷引起的肾功能障碍。通过测定硫代巴比妥酸反应物质、超氧阴离子产生和降低的谷胱甘肽水平来确定大鼠肾脏中的氧化应激。此外，进行羟脯氨酸测定以评估砷中毒大鼠的肾纤维化。苏木精-伊红和苦天狼疮红染色揭示了大鼠肾脏的病理改变。通过免疫组织化学测定肾内皮一氧化氮合酶（eNOS）的表达。同时施用甜菜碱可消除砷诱导的大鼠肾脏生化和组织学变化。甜菜碱治疗显着减弱了砷诱导的肾 eNOS 表达下降。总之，甜菜碱对亚砷酸钠引起的肾功能障碍具有保护作用，这可能归因于其抗氧化活性和调节大鼠肾脏中肾 eNOS 的表达。同时施用甜菜碱可消除砷诱导的大鼠肾脏生化和组织学变化。甜菜碱治疗显着减弱了砷诱导的肾 eNOS 表达下降。总之，甜菜碱对亚砷酸钠引起的肾功能障碍具有保护作用，这可能归因于其抗氧化活性和调节大鼠肾脏中肾 eNOS 的表达。同时施用甜菜碱可消除砷诱导的大鼠肾脏生化和组织学变化。甜菜碱治疗显着减弱了砷诱导的肾 eNOS 表达下降。总之，甜菜碱对亚砷酸钠引起的肾功能障碍具有保护作用，这可能归因于其抗氧化活性和调节大鼠肾脏中肾 eNOS 的表达。