Amudha Ganapathy, Josephine Anthony, Mythili Yenjerla, Sundarapandiyan Rajaguru, Varalakshmi Palaninathan
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600 113, India.
Eur J Pharmacol. 2007 Oct 1;571(2-3):209-14. doi: 10.1016/j.ejphar.2007.05.047. Epub 2007 Jun 9.
The present study was designed to evaluate the possible beneficial effect of lipoic acid in preventing the renal damage induced by cyclosporine A in rats. Male albino rats of Wistar strain were divided into four groups and treated as follows. Two groups received cyclosporine A by oral gavage (25 mg/kg/body weight) for 21 days to induce nephrotoxicity, one of which simultaneously received lipoic acid treatment (20 mg/kg body weight) for 21 days. A vehicle (olive oil) and a lipoic acid drug control were also included. Cyclosporine A induced renal damage was evident from the decreased activities of tissue marker enzymes (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and decreased activities of ATPases (Na+, K+-ATPase, Ca2+-ATPase and Mg2+ ATPase). An apparent increase in the levels of serum constituents (urea, uric acid and creatinine) and urinary marker enzymes (N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galactosidase, cathepsin-D and gamma-glutamyl transpeptidase) along with significant decline in creatinine clearance were seen in the cyclosporine treated rats, which was reversed upon treatment with lipoic acid. Ultrastructural observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the morphological lesions in renal tissue. Hence, this study clearly exemplifies that lipoic acid might be an ideal choice against cyclosporine A induced cellular abnormalities.
本研究旨在评估硫辛酸对预防环孢素A诱导的大鼠肾损伤可能产生的有益作用。将雄性Wistar品系白化大鼠分为四组，并进行如下处理。两组通过灌胃给予环孢素A（25 mg/kg体重），持续21天以诱导肾毒性，其中一组同时接受硫辛酸治疗（20 mg/kg体重），持续21天。还设置了一个赋形剂（橄榄油）对照组和一个硫辛酸药物对照组。从组织标记酶（碱性磷酸酶、酸性磷酸酶、乳酸脱氢酶、天冬氨酸转氨酶和丙氨酸转氨酶）活性降低以及ATP酶（Na + ，K + -ATP酶、Ca 2+ -ATP酶和Mg 2+ -ATP酶）活性降低可以明显看出环孢素A诱导的肾损伤。在接受环孢素治疗的大鼠中，血清成分（尿素、尿酸和肌酐）水平以及尿标记酶（N-乙酰-β-D-氨基葡萄糖苷酶、β-葡萄糖苷酶、β-半乳糖苷酶、组织蛋白酶-D和γ-谷氨酰转肽酶）明显升高，同时肌酐清除率显著下降，而用硫辛酸治疗后这些变化得到逆转。超微结构观察结果也与上述异常变化一致。硫辛酸有效地逆转了这些异常生化变化，并使肾组织中的形态学损伤最小化。因此，本研究清楚地表明，硫辛酸可能是对抗环孢素A诱导的细胞异常的理想选择。
