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

被引:16
|
作者
Zhang, Tianya [1 ]
Zhang, Dong [1 ]
Zhang, Zhihong [1 ,2 ]
Tian, Jiaxin [1 ]
An, Jingwen [1 ]
Zhang, Wang [1 ]
Ben, Ying [1 ,2 ]
机构
[1] Hebei Univ Chinese Med, Shijiazhuang, Hebei, Peoples R China
[2] Hebei Univ Chinese Med, Hebei Key Lab Integrat Med Liver Kidney Patterns, Shijiazhuang, Hebei, Peoples R China
来源
HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM | 2023年 / 22卷 / 01期
关键词
Alpha-lipoic acid; Diabetic peripheral neuropathy; Dorsal root ganglia; Apoptosis; Oxidative stress; DISEASE;
D O I
10.1007/s42000-022-00413-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:95 / 105
页数:11
相关论文
共 50 条
  • [21] Symptomatic and pathogenetic treatment of diabetic neuropathy Role of alpha-lipoic acid
    Gemignani, Franco
    NEURAL REGENERATION RESEARCH, 2010, 5 (10) : 781 - 788
  • [22] Effect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review
    Abubaker, Saleh A.
    Alonazy, Abdulaziz M.
    Abdulrahman, Albasseet
    CUREUS JOURNAL OF MEDICAL SCIENCE, 2022, 14 (06)
  • [24] Assessment of the role of alpha-lipoic acid against the oxidative stress of induced iron overload
    Ali, Yasser F.
    Desouky, Omar S.
    Selim, Nabila S.
    Ereiba, Khairy. M.
    JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES, 2015, 8 (01) : 26 - 35
  • [25] The Effect of Alpha-Lipoic Acid on Diabetic Peripheral Neuropathy and the Upcoming Depressive Disorders of Type II Diabetics
    Karalis, Dimitrios T.
    Karalis, Tilemachos
    Karalis, Stergios
    Kleisiari, Angeliki S.
    Malakoudi, Foteini
    Maimari, Konstantina Eleni, V
    CUREUS JOURNAL OF MEDICAL SCIENCE, 2021, 13 (01)
  • [26] ALPHA-LIPOIC ACID TREATMENT INCREASES SERUM PROGRANULIN LEVEL IN DIABETIC NEUROPATHY
    Nadro, B.
    Sztanek, F.
    Lorincz, H.
    Szentpeteri, A.
    Molnar, A.
    Ildiko, S.
    ATHEROSCLEROSIS, 2020, 315 : E201 - E202
  • [27] Protective Effect of Alpha-lipoic Acid Against Lead Acetate-Induced Oxidative Stress in the Bone Marrow of Rats
    Haleagrahara, Nagaraja
    Jackie, Tan
    Chakravarthi, Srikumar
    Kulur, Anupama Bangra
    INTERNATIONAL JOURNAL OF PHARMACOLOGY, 2011, 7 (02) : 217 - 227
  • [28] Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats
    Budin, Siti Balkis
    Othman, Faizah
    Louis, S. R.
    Abu Bakar, M.
    Radzi, M.
    Osman, K.
    Das, S.
    Mohamed, J.
    ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY, 2009, 50 (01): : 23 - 30
  • [29] PROTECTIVE EFFECT OF ALPHA-LIPOIC ACID ON CYPERMETHRIN-INDUCED OXIDATIVE STRESS IN WISTAR RATS
    Mignini, F.
    Nasuti, C.
    Fedeli, D.
    Mattioli, L.
    Cosenza, M.
    Artico, M.
    Gabbianelli, R.
    INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2013, 26 (04) : 871 - 881
  • [30] Alpha-lipoic acid and oxidative stress in the physical effort of variable intensity
    Ghibu, S.
    Muresan, A.
    Morgovan, C.
    FREE RADICAL RESEARCH, 2006, 40 : S157 - S157