Role of DL alpha-lipoic acid in gentamicin induced nephrotoxicity.
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, Ca(2+)-ATPase, Mg(2+)-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.
Sandhya
P
P
Department of Medical Biochemistry, Post Graduate Institute of Basic Medical Sciences, Madras, India.
Mohandass
S
S
Varalakshmi
P
P
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects*; D005943:Gluconeogenesis; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007441:Intubation, Gastrointestinal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000494:pharmacology*
D005839:Gentamicins; D008063:Thioctic Acid; D000429:Alcohol Oxidoreductases; D006593:Hexokinase; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; D005634:Fructose-Bisphosphate Aldolase; D005956:Glucose-6-Phosphate Isomerase