Evaluation of the effects of alpha-lipoic acid on cyclosporine-induced memory dysfunction and cellular immunosuppression in rats.

Background

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Purpose

Cyclosporine A (CsA) is used to control autoimmune reactions and prevent organ rejection, but its clinical application is limited by neurotoxicity and nephrotoxicity. This study investigated the neuroprotective effects of alpha-lipoic acid (ALA), an antioxidant, anti-inflammatory, and immunomodulatory agent, against CsA‑induced memory impairment and immunosuppression in rats. STUDY

Design

Male rats were divided into seven groups (n=6 per group): Sham, CsA (25 mg/kg, on alternate days, 7 doses), CsA + ALA (20, 40, and 80 mg/kg), CsA + rivastigmine (1 mg/kg), and ALA alone (80 mg/kg). All treatments were administered intraperitoneally for 14 days. Spatial memory was assessed using the Morris Water Maze (MWM). Analyses included hippocampal histopathology, oxidative stress markers (MDA, GSH), and western blot (BDNF, CREB, p‑CREB). Lymphocytes' viability and cytokine secretion (IFN‑γ, IL‑10) in the supernatant of cultured lymphocytes were assessed using resazurin and enzyme-linked immunosorbent assay, respectively. Renal function was evaluated by measuring serum BUN and creatinine.

Results

CsA impaired spatial memory in the MWM test. In the hippocampus, CsA increased MDA levels and reduced GSH levels, correlating with ischemic neuronal changes, perineural and perivascular edema, and hyperemia. Furthermore, CsA downregulated BDNF expression and the p-CREB/CREB ratio. Concurrently, CsA decreased lymphocyte viability and the secretion of both IFN‑γ and IL‑10, and increased serum BUN levels. Conversely, ALA treatment markedly improved MWM performance, restored antioxidant capacity, upregulated BDNF expression and p-CREB/CREB levels, ameliorated histopathological damage, partially restored lymphocyte viability and cytokine production, and decreased BUN levels.

Conclusion

These findings suggest that ALA may exert neuroprotective effects against CsA-induced memory dysfunction while preserving the inhibitory effects of CsA on lymphocytes.