Background: Alzheimer's disease (AD) is a neurodegenerative disorder that progresses and is distinguished by impaired cellular homeostasis, oxidative stress, and neuroinflammation. The cellular defense against oxidative injury is influenced by the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1). Aim: This study aimed to assess potential protective L-carnitine effects anti aluminum chloride (AlCl₃)-induced Alzheimer’s pathology in rats, with a focus on Nrf2/HO-1 modulation signaling pathway. Materials and Methods:24 Adult male rats were randomly divided into control, AlCl₃ group, L-carnitine-protected, and AlCl₃ + L-carnitine co-administered groups. Cognitive performance was assessed using behavioral tests. Brain tissue was examined for oxidative stress markers including malondialdehyde (MDA) and superoxide dismutase (SOD) activity, phosphorylated tau (p-tau) levels, histopathological changes, and Nrf2/HO-1 gene expression using RT-PCR. Results: AlCl₃ administration significantly impaired cognitive functions, increased oxidative stress, and downregulated Nrf2/HO-1 expression. L-carnitine treatment markedly ameliorated behavioral deficits, reduced lipid peroxidation, enhanced antioxidant defense, and upregulated Nrf2 and HO-1 expression. Conclusion: L-carnitine exerts neuroprotective effects versus AlCl₃-induced Alzheimer’s-like changes in rats, potentially through Nrf2/HO-1 activation pathway. These findings propose that L-carnitine may represent a promising therapeutic candidate for mitigating oxidative stress and neurodegeneration in AD. |
