Protective Potentials of Alpha-Lipoic Acid against Ionizing Radiation-Induced Brain Damage in Rats
Ji Xu, Ameer A. Alameri, Rahman S. Zabibah, Gamal A. Gabr, Andrés Alexis Ramírez‐Coronel, Hamed Bagheri, Razzagh Abedi‐Firouzjah
Abstract
Background. This study was aimed at determining the effects of alpha-lipoic acid on ionizing irradiation-induced oxidative damage and apoptosis in the brain of rats. Methods. The animals were exposed to whole-brain X-radiation with a 15 Gy single dose in the absence or presence of alpha-lipoic acid (200 mg/kg body weight) pretreatment for one week. The rats were divided into four groups (5 rats in each group): vehicle control, alpha-lipoic acid alone (ALA), radiation alone (RAD), and radiation plus alpha-lipoic acid (RAD+ALA). In the next stage, malondialdehyde (MDA), nitric oxide, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the brain tissue of the rats were measured. Furthermore, the Western blot analysis technique was performed to assess the NOX2, NOX4, and caspase-3 protein expression levels. Results. Twenty-four hours after the irradiation, MDA and nitric oxide levels in the irradiated rats were significantly higher than those in the control group ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>p</a:mi> <a:mo><</a:mo> <a:mn>0.001</a:mn> </a:math> ); however, the pretreatment with alpha-lipoic acid resulted in a significant reduction in these stress oxidative markers ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>p</c:mi> <c:mo><</c:mo> <c:mn>0.05</c:mn> </c:math> ). Moreover, a significant decrease in CAT, SOD, and GPx levels was observed in the radiation group alone compared to the control group ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>p</e:mi> <e:mo><</e:mo> <e:mn>0.01</e:mn> </e:math> ); in contrast, the activities of these antioxidant enzymes significantly increased in the radiation plus alpha-lipoic acid group in comparison to the radiation group alone ( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>p</g:mi> <g:mo><</g:mo> <g:mn>0.05</g:mn> </g:math> ). The results of Western blot analysis revealed that NOX2, NOX4, and caspase-3 protein expressions significantly elevated in the irradiated rats compared to the control group ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>p</i:mi> <i:mo><</i:mo> <i:mn>0.001</i:mn> </i:math> ). The pretreatment with alpha-lipoic acid could significantly decrease the expression levels of NOX2, NOX4, and caspase-3 in comparison with the radiation group alone ( <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>p</k:mi> <k:mo><</k:mo> <k:mn>0.05</k:mn> </k:math> ). Conclusion. According to the obtained findings, it can be mentioned that the alpha-lipoic acid pretreatment could mitigate the ionizing irradiation-induced oxidative damage and apoptosis in the brain of the rats.