Anti-apoptotic and neuroprotective effects of alpha-lipoic acid on spinal cord ischemia–reperfusion injury in rabbits

Abstract

Radical oxygen species produced after injury counteracts antioxidant activity and frequently causes severe oxidative stress for the tissues. Alpha-lipoic acid is a powerful metabolic antioxidant with immunomodulatory effects which provides neuroprotection. The aim of this study is to investigate the neuroprotective and anti-apoptotic effects of alpha-lipoic acid on spinal cord ischemia-reperfusion. Twenty-four adult, male, New Zealand rabbits were divided into sham (n = 8), control (n = 8), and treatment groups (n = 8). The abdominal aorta was clamped for 30 min by an aneurysm clip, approximately 1 cm below the renal artery and 1 cm above the iliac bifurcation in control and treatment groups. Only laparotomy was performed in the sham group. Twenty-five cubic centimeters of saline in control group and 100 mg/kg lipoic acid were administered intraperitoneally in the treatment group after closure of the incision. The animals were killed 48 h later. Spinal cord segments between L2 and S1 were harvested for analysis. Levels of nitric oxide, glutathione, malondialdehyde, advanced oxidation protein products, and superoxide dismutase were analyzed as markers of oxidative stress and inflammation. Caspase-3 activity was analyzed to detect the effect of lipoic acid on apoptosis. In all measured parameters of oxidative stress, administration of lipoic acid significantly demonstrated favorable effects. Both plasma and tissue levels of nitric oxide, glutathione, malondialdehyde, and advanced oxidation protein products significantly changed in favor of antioxidant activity. There was no significant difference between the plasma superoxide dismutase levels of the groups. Histopathological evaluation of the tissues also demonstrated significant decrease in cellular degeneration and infiltration parameters after lipoic acid administration. However, lipoic acid has no effect on caspase-3 activity. Although further studies considering different dose regimens and time intervals are required, the results of the present study prove that alpha-lipoic acid has favorable effects on experimental spinal cord ischemia-reperfusion injury.