The Effect of Alpha-Lipoic Acid on Preventing Amikacin-Induced DNA Damage in Rats

Abstract

Amikacin (AK) is a preferred antibacterial drug, but it is associated with significant dose dependent toxic side effects. Alpha-lipoic acid (ALA) is an effective antioxidant which protects cellular macromolecules against various drug induced toxicities. This study was designed to determine the effects of AK on the DNA of rat lymphocytes, and the possible protective effects of ALA on genotoxicity induced by AK. Three different groups of rats (n = 8) were formed: (1) Control: administered saline, (2) AK: administered 1.2 g/kg, single dose, intraperitoneally, and (3) ALA: administered 100 mg/kg, p.o. and AK combination (ALA 1 day before the AK for 5 days). DNA damage through comet assay was analyzed in peripheral blood lymphocytes of rats. Total oxidant system (TOS), total antioxidant system (TAS), and ischemia-modified albumin (IMA) as serum oxidative stress markers were measured in blood serum. AK administration to rats increased DNA damage, IMA and TOS levels (p = 0.0002, p = 0.013, p = 0.048, respectively), but decreased TAS levels (p = 0.011). ALA administration before AK injection caused a significant increase in TAS levels (p = 0.000), and caused a significant decrease in TOS, IMA, and DNA damage levels (p = 0.000, p = 0.003, 0.044, respectively). The present findings showed that AK caused DNA damage in lymphocytes of rats and ALA provided a protective effect against AK induced DNA damage by balancing the oxidant-antioxidant status, and it may therefore improve the therapeutic effects of AK.