Sivaprasad Thylambal Rajagopalan, Malarkodi Saroja Palanichamy, Varalakshmi Palaninathan
Department of Medical Biochemistry, Dr. A.L.M. PGIBMS, University of Madras, Taramani Campus, Chennai 600113, India.
Chem Biol Interact. 2004 Apr 15;147(3):259-71. doi: 10.1016/j.cbi.2004.01.004.
The combined therapeutic potentials of lipoic acid and dimercaptosuccinic acid were compared against their sole administrations in restoring the altered lead sensitive indices in urine and isolated renal brush-border preparations. Toxicity was induced in male albino rats (Wistar strain) by administering lead acetate (0.2%) in drinking water for 5 weeks, followed by therapy comprising lipoic acid (25 mg/kg body weight) and dimercaptosuccinic acid (20 mg/kg body weight) solely as well as combined during the 6th week. Changes in kidney weights encountered upon lead administration improved after therapy with lipoic acid and dimercaptosuccinic acid. Renal integrity was assessed by measuring the activities of alkaline phosphatase, acid phosphatase, lactate dehydrogenase, leucine aminopeptidase, N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transferase and beta-glucuronidase in urine along with some urinary constituents (urea, uric acid, creatinine, protein and phosphorous). The effects of lead were also studied on isolated brush-border enzymes (alkaline phosphatase, acid phosphatase, gamma-glutamyl transferase and beta-glucuronidase) that showed a decline upon its administration. Increased activities of urinary enzymes were accompanied by increase in the urinary constituents. Increase in renal lead content was paralleled by a drastic fall in the renal delta-aminolevulinic acid dehydratase and a rise in urinary lead levels. Relative to the administration of lead, the combined therapy showed betterment on the renal integrity with respect to the functional parameters assessed, thereby indicating its efficacy over the monotherapies.
比较了硫辛酸和二巯基丁二酸联合使用与单独使用时,恢复尿液和离体肾刷状缘制剂中改变的铅敏感指标的治疗潜力。通过在饮用水中给予醋酸铅(0.2%)5周,诱导雄性白化大鼠(Wistar品系)产生毒性,随后在第6周进行治疗,治疗药物包括单独使用硫辛酸(25mg/kg体重)和二巯基丁二酸(20mg/kg体重)以及联合使用这两种药物。给予铅后出现的肾脏重量变化,在使用硫辛酸和二巯基丁二酸治疗后得到改善。通过测量尿液中碱性磷酸酶、酸性磷酸酶、乳酸脱氢酶、亮氨酸氨肽酶、N-乙酰-β-D-氨基葡萄糖苷酶、γ-谷氨酰转移酶和β-葡萄糖醛酸酶的活性以及一些尿液成分(尿素、尿酸、肌酐、蛋白质和磷)来评估肾脏完整性。还研究了铅对离体刷状缘酶(碱性磷酸酶、酸性磷酸酶、γ-谷氨酰转移酶和β-葡萄糖醛酸酶)的影响,这些酶在给予铅后活性下降。尿液酶活性增加伴随着尿液成分增加。肾脏铅含量增加与肾脏δ-氨基乙酰丙酸脱水酶急剧下降和尿铅水平升高同时发生。相对于给予铅的情况,联合治疗在评估的功能参数方面对肾脏完整性显示出更好的改善,从而表明其疗效优于单一疗法。