Fatima S, Arivarasu N A, Banday A A, Yusufi A N K, Mahmood R
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India.
Hum Exp Toxicol. 2005 Dec;24(12):631-8. doi: 10.1191/0960327105ht585oa.
Chromium is widely used in industry but exposure to chromium compounds in the workplace can result in nephrotoxicity. Various nephrotoxicants affect the brush border membrane (BBM) lining the epithelial cells of the proximal tubule, but there have been no studies regarding the effect of potassium dichromate (K2Cr2O7), a hexavalent chromium compound, on renal BBM. In the present work, the effect of administering a single intraperitoneal dose (15 mg/kg body weight) of K2Cr2O7 on rat renal BBM enzymes and inorganic phosphate (Pi) transport was studied. The animals were administered normal saline (control) or K2Cr2O7 and sacrificed 1, 2, 4 and 8 days after treatment. K2Cr2O7 induced reversible damage to the rat kidney function as indicated by serum creatinine (Scr) and urea nitrogen levels. The activities of BBM marker enzymes were significantly decreased in isolated BBM vesicles (BBMV) and homogenates of cortex and medulla on 1, 2 and 4 days after administration of K2Cr2O7 with complete recovery to control values after 8 days. The decrease in the activities of the enzymes was mainly due to changes in maximum velocity (V(max)) values, while the Michaelis constant (Km) remained unchanged. The sodium dependent Pi transport across BBMV was reduced by 50% after treatment with K2Cr2O7. Thus, the administration of a single dose of K2Cr2O7 leads to impairment in the functions of renal BBM. These results suggest that the nephrotoxicity of K2Cr2O7 may be mediated, at least in part, by its effect on renal BBM.
铬在工业中广泛使用,但在工作场所接触铬化合物可导致肾毒性。各种肾毒物会影响近端小管上皮细胞内衬的刷状缘膜(BBM),但关于六价铬化合物重铬酸钾(K2Cr2O7)对肾BBM的影响尚无研究。在本研究中,研究了腹腔注射单剂量(15 mg/kg体重)K2Cr2O7对大鼠肾BBM酶和无机磷酸盐(Pi)转运的影响。给动物注射生理盐水(对照)或K2Cr2O7,并在治疗后1、2、4和8天处死。血清肌酐(Scr)和尿素氮水平表明,K2Cr2O7对大鼠肾功能造成了可逆性损伤。在给予K2Cr2O7后1、2和4天,分离的BBM囊泡(BBMV)以及皮质和髓质匀浆中BBM标记酶的活性显著降低,8天后完全恢复至对照值。酶活性的降低主要是由于最大速度(V(max))值的变化,而米氏常数(Km)保持不变。用K2Cr2O7处理后,钠依赖性Pi跨BBMV的转运减少了50%。因此,单剂量给予K2Cr2O7会导致肾BBM功能受损。这些结果表明,K2Cr2O7的肾毒性可能至少部分是由其对肾BBM的作用介导的。