Role of DL ?-lipoic acid in gentamicin induced nephrotoxicity

Abstract

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.

Time dependent effects of gentamicin on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in rat kidney tissues

“…Glutathione (GSH) and its redox cycle enzymes e.g., SOD, catalase, GSH-Px are important cellular defense system against oxidative stress. It has been reported that GM suppresses antioxidant defense enzymes and increases lipid peroxidation in the kidney (Ali and Bashir, 1996;Parlakpinar et al, 2004;Sandhya et al, 1995). The present results confirm earlier findings (Walker et al, 1999;Yazar et al, 2003;Karahan et al, 2005) and show that GM administration to normal rats caused severe damage to renal tissues most likely by ROS mediated mechanism as evident by decreased activities of above antioxidant enzymes and total SH levels that led to increased lipid peroxidation (LPO).…”

Antioxidants: A Possible Role in Kidney Protection

“…Experimental studies demonstrated that ALA supplementation might decrease renal expression of endothelin-1 [109], fibronectin and collagen IV [110]. The protective influence of ALA against aminoglycoside-, and cisplatin-induced nephrotoxicity was shown in animal studies [111,112]. ALA was also found to attenuate deterioration of renal function in a model of ischemia/reperfusion injury [109].…”

Evaluation of Efficacy of Vitamin E andN-Acetyl Cysteine in Gentamicin-Induced Nephrotoxicity in Rats

“…Aminoglycoside antibiotics impair the function of mitochondrial enzymes for the gluconeogenesis, ammoniagenesis, and tricarboxylic acid oxidation pathways 21,22 ; in addition aminoglycoside antibiotics also downregulate the sodium-dependent glucose transport system 23,24 and reduce mRNA expression and protein levels of serum glutamate transaminase 1. This reduced reabsorption of glucose, resulting in increased urinary glucose excretion.…”