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. 2021 Aug;39(4):1103-1115.
doi: 10.1007/s12640-021-00348-8. Epub 2021 Mar 10.

Alpha-Lipoic Acid Attenuates Cadmium- and Lead-Induced Neurotoxicity by Inhibiting Both Endoplasmic-Reticulum Stress and Activation of Fas/FasL and Mitochondrial Apoptotic Pathways in Rat Cerebral Cortex

Yan Yuan #  1   2 , Shi Wen Zhao #  1   2 , Shuang Quan Wen  1   2 , Qiao Ping Zhu  1   2 , Li Wang  1   2 , Hui Zou  1   2 , Jian Hong Gu  1   2 , Xue Zhong Liu  1   2 , Jian Chun Bian  1   2 , Zong Ping Liu  3   4
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Alpha-Lipoic Acid Attenuates Cadmium- and Lead-Induced Neurotoxicity by Inhibiting Both Endoplasmic-Reticulum Stress and Activation of Fas/FasL and Mitochondrial Apoptotic Pathways in Rat Cerebral Cortex

Yan Yuan et al. Neurotox Res. 2021 Aug.

Abstract

Although many studies have reported toxic effects of cadmium (Cd) and lead (Pb) in the central nervous system, few studies have investigated the combined toxicity of Cd and Pb. The mechanisms by which these combined heavy metals induce toxicity, as well as effective means to exert neuroprotection from these agents, remain poorly understood. To investigate the protective effects of alpha-lipoic acid (α-LA) on Cd- and/or Pb-induced cortical damage in rats, 48 Sprague-Dawley rats were exposed to drinking water containing 50 mg/L of Cd and/or 300 mg/L of Pb for 12 weeks, in the presence or absence of α-LA co-treatment (50 mg/kg) via gavage. We observed that exposure to Cd and/or Pb decreased the brain weight/body weight ratio and increased Cd and/or Pb contents as well as ultrastructural damage to the cerebral cortex. Cd and/or Pb also induced endoplasmic-reticulum (ER) stress and activated Fas (CD95/APO-1)/Fas ligand (FasL) and mitochondrial apoptotic pathways. Furthermore, co-treatment of Cd and Pb further exacerbated part of these phenotypes than treatment of Cd or Pb alone. However, simultaneous supplementation with α-LA attenuated Cd and/or Pb-induced neurotoxicity by increasing the brain weight/body weight ratio, reducing Cd and/or Pb contents, ameliorating both nuclear/mitochondrial damage and ER stress, and attenuating activation of Fas/FasL and mitochondrial apoptotic pathways. Collectively, our results indicate that the accumulation of Cd and/or Pb causes cortical damage and that α-LA exerts protection against Cd- and/or Pb-induced neurotoxicity. These findings highlight that α-LA may be exploited for the treatment and prevention of Cd- and/or Pb-induced neurotoxicity.

Keywords: Cadmium; Endoplasmic-reticulum stress; Fas/FasL apoptotic pathway; Lead; Mitochondrial apoptotic pathway; Rat cerebral cortex.

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References

    1. Alhusaini A, Fadda L, Hasan IH, Ali HM, El Orabi NF et al (2019) Arctium lappa Root Extract Prevents Lead-Induced Liver Injury by Attenuating Oxidative Stress and Inflammation, and Activating Akt/GSK-3beta Signaling. Antioxidants (Basel) 8:582. https://doi.org/10.3390/antiox8120582
    1. Ambrosi N, Guerrieri D, Caro F, Sanchez F, Haeublein G et al (2018) Alpha lipoic acid: a therapeutic strategy that tend to limit the action of free radicals in transplantation. Int J Mol Sci 19:102. https://doi.org/10.3390/ijms19010102 - DOI - PMC
    1. Barkur RR, Bairy LK (2015) Assessment of oxidative stress in hippocampus, cerebellum and frontal cortex in rat pups exposed to lead (Pb) during specific periods of initial brain development. Biol Trace Elem Res 164:212-218. https://doi.org/10.1007/s12011-014-0221-3
    1. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2:326–332. https://doi.org/10.1038/35014014 - DOI - PubMed
    1. Chen S, Liu G, Long M, Zou H, Cui H (2018) Alpha lipoic acid attenuates cadmium-induced nephrotoxicity via the mitochondrial apoptotic pathways in rat. J Inorg Biochem 184:19–26. https://doi.org/10.1016/j.jinorgbio.2018.04.001 - DOI - PubMed

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