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Alpha-lipoic acid activates AMPK to protect against oxidative stress and apoptosis in rats with diabetic peripheral neuropathy

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Abstract

Purpose

To investigate the AMPK pathway–mediated effect of alpha-lipoic acid (ALA) on the dorsal root ganglia (DRGs) of rats with diabetic peripheral neuropathy (DPN) and to attempt to elucidate the underlying mechanism.

Methods

Sprague-Dawley rats (n = 15) were randomly divided into three groups. The control group was fed a standard diet, and the other groups were fed a high-carbohydrate/high-fat diet. Diabetes was established by a single streptozotocin (STZ) (30 mg/kg) injection, and control rats were injected with an equal volume of citrate buffer. ALA (60 mg/kg/day) was administered for 12 weeks. The nerve conduction velocity (NCV) of the sciatic nerve was measured. Glutathione (GSH) and malondialdehyde (MDA) concentrations in serum were measured with the thiobarbituric acid method and biochemistry. Pathological changes in the rat DRGs were observed. AMPK, phospho-AMPK (p-AMPK), nuclear factor erythroid-2-related factor 2 (Nrf2), phospho-nuclear factor erythroid-2-related factor 2 (p-Nrf2), heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1), Forkhead box O3 (FoxO3a), phospho-Forkhead box O3 (p-FoxO3a), and Bcl-2 interacting mediator of cell death (Bim) expression levels were assessed by immunohistochemistry and western blotting.

Results

ALA improved the motor NCV (MNCV) and sensory NCV (SNCV) of rats with DPN and reduced their mechanical pain threshold. ALA increased serum GSH concentrations and decreased serum MDA concentrations. Additionally, AMPK was activated by ALA. Nrf2, p-Nrf2, HO-1, and NQO1 expression was upregulated, while FoxO3a, p-FoxO3a, and Bim expression was downregulated. ALA reduced oxidative stress and apoptosis in DRG.

Conclusion

ALA alleviates DPN and improves peripheral nerve function. ALA reduces oxidative stress by activating Nrf2 through AMPK and inhibits FoxO3a and Bim thereby reducing neuronal apoptosis.

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Funding

This work was supported by the National Natural Science Foundation [grant numbers 81803922] funded by CHINA and Construction Program of new research and development platform and institution, Hebei Province Innovation Ability Promotion Plan (No. 20567624H).

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Authors and Affiliations

  1. Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China

    Tianya Zhang, Dong Zhang, Zhihong Zhang, Jiaxin Tian, Jingwen An, Wang Zhang & Ying Ben

  2. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China

    Zhihong Zhang & Ying Ben

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  1. Tianya Zhang
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  2. Dong Zhang
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Correspondence to Ying Ben.

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Zhang, T., Zhang, D., Zhang, Z. et al. Alpha-lipoic acid activates AMPK to protect against oxidative stress and apoptosis in rats with diabetic peripheral neuropathy. Hormones 22, 95–105 (2023). https://doi.org/10.1007/s42000-022-00413-7

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