Effects of alpha-lipoic acid on skeletal muscle ischemia-reperfusion injury in mice

Abstract

Aim: The main problem in the treatment of cardiovascular diseases, which is the most common cause of death in the world today, is reperfusion injury. In our study, we investigated the effects of alpha-lipoic acid on lower limb ischemia-reperfusion injury.
Methods: In this study, 30 male Swiss breed albino mice weighing 45-65 g were used. Mice were randomly divided into 5 groups (Control group (C), Dimethyl Sulfoxide (DMSO) group, ischemia-reperfusion (IR) group, alpha-lipoic acid control group (ALA), alpha-lipoic acid - IR group (ALA+IR)), 6 mice in each group. All groups were administered 100 IU/kg intravenous heparin bolus 30 minutes before the procedure. Lower limb ischemia (2 hours) and reperfusion (2 hours) protocols were applied to the IR and ALA+IR groups by clamping the main femoral artery. Alpha-lipoic acid was administered to ALA and ALA+IR groups 1 hour before the experimental procedure (100 mg/kg intraperitoneal). After the experiment protocol, the lower limb gastrocnemius muscles were collected from the sacrificed mice and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), Myeloperoxidase (MPO) and Malondialdehyde (MDA) levels were determined in the tissue. In addition, edema, necrosis, and inflammatory cell infiltration levels in the skeletal muscle were determined by histologic grading, and apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method.
Results: TAS measurements of ALA group subjects were higher than the control group (P=0.01). The TOS level of the ALA+IR group was lower than the IR group (P=0.01), but higher than the C, ALA, and DMSO groups. The OSI index of the IR group was significantly higher than the ALA+IR group (P=0.01). It was observed that the IR group was at higher levels than the ALA+IR group (P=0.01). MDA measurements of IR group subjects were higher than that of the C, ALA, DMSO, ALA+IR groups (P=0.01). Edema of the IR and ALA+IR group subjects were higher than the C, ALA, DMSO groups (P=0.01). Necrosis measurements of IR and ALA+IR group subjects were higher than C, ALA, DMSO groups (P=0.01). Inflammatory cell infiltration measurements of IR and ALA+IR group subjects were higher than C, ALA, DMSO groups (P=0.01). Apoptosis level was significantly lower in the ALA+IR group than in the IR group. (P=0.01).
Conclusion: The results showed us that alpha-lipoic acid has a protective effect against oxidative damage, inflammation, and apoptosis in the tissue in lower limb ischemia-reperfusion.