ROLE OF DL-ALPHA-LIPOIC ACID IN GENTAMICIN-INDUCED NEPHROTOXICITY

被引:35
作者
SANDHYA, P [1 ]
MOHANDASS, S [1 ]
VARALAKSHMI, P [1 ]
机构
[1] POSTGRAD INST BASIC MED SCI,DEPT MED BIOCHEM,MADRAS 600113,TAMIL NADU,INDIA
关键词
GENTAMICIN; LIPOIC ACID; RAT KIDNEY; GLYCOLYTIC; GLUCONEOGENIC;
D O I
10.1007/BF00925707
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The effect of DL alpha-lipoic acid on the nephrotoxic potential of gentamicin was examined. Intraperitoneal injection of gentamicin (100 mg/kg/day) to rats resulted in decreased activity of the glycolytic enzymes-hexokinase, phosphoglucoisomerase, aldolase and lactate dehydrogenase. The two gluconeogenic enzymes-glucose-6-phosphatase and fructose-1,6-diphosphatase, the transmembrane enzymes namely the Na+, K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and the brushborder enzyme alkaline phosphatase, also showed decreased activities. This decrease in the activities of ATPases and alkaline phosphatase suggests basolateral and brush border membrane damage. Decreased activity of the TCA cycle enzymes isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH), suggests a loss in mitochondrial integrity. These biochemical disturbances were effectively counteracted by lipoic acid administration. Lipoic acid administration by gastric intubation at two different concentrations (10 mg and 25 mg/kg/day) brought about an increase in the activity of the glycolytic enzymes, ATPases and the TCA cycle enzymes. The gluconeogenic enzymes however showed a further decrease in their activities at both the concentrations of lipoic acid administered. These observations shed light on the nephroprotective action of lipoic acid against experimental aminoglycoside toxicity and the protection afforded at 25 mg/kg/day of lipoic acid was noted to be higher than that at 10 mg level.
引用
收藏
页码:11 / 17
页数:7
相关论文
共 33 条
[1]  
Walter A.M., Heilmeier L., Antibiotika-Fibel, (1975)
[2]  
GinnShelburne J., Trump B., Disorders of cell Volume regulation, Am J Pathol, 53, pp. 1041-1071, (1968)
[3]  
Horio M., Fukuhara Y., Orita Y., Akanishi T., Nakahara H., Moriyama T., Kumada T., Gentamicin inhibits Na<sup>+</sup> dependent glucose transport in rabbit kidney brush border membrane vesicles, Biochim Biophys Acta, 858, pp. 153-160, (1986)
[4]  
Biber J., Hauser H., The role of SH-group in the concentrative transport of D-glucose into brush border membrane vesicles, FEBS Lett, 108, 2, pp. 451-456, (1979)
[5]  
Masayuki T., Yukihiko A., Asaichi I., Seishi T., Inhibition of alkaline phosphatase activity and D-glucose uptake in rat renal brush border membrane vesicles by aminoglycosides, Biochim Biophys Acta, 903, pp. 31-36, (1987)
[6]  
Belly G.D., Willia R.J., Effect of lipoic acid on the growth rate of young rats, Arch Biochem Biophys, 55, pp. 587-588, (1955)
[7]  
Jayanthi S., Jayanthi G., Varalakshmi P., Effect of DL α-lipoic acid on some carbohydrate metabolising enzymes in stone forming rats, Biochem Int, 25, 1, pp. 123-136, (1991)
[8]  
Haugaard N., Haugaard E.S., Stimulation of glucose utilisation by thiotic acid in rat diaphragm incubated in vitro, Biochim Biophys Acta, 222, pp. 583-586, (1970)
[9]  
Gandhi V.M., Wagh S.S., Nataraj C.V., Menon K.K.G., Lipoic acid and diabetes II. Mode of action of lipoic acid, J Bio Sci, 9, pp. 117-127, (1985)
[10]  
Bashan N., Burdett E., Guma A., Klip A., Effect of Thioctic acid on glucose transport, The role of antioxidants in Diabetes mellitus. Oxygen radicals and antioxidants in Diabetes, pp. 221-229, (1993)