Abstract
Lead (Pb) is a common heavy metal contaminant in the environment, and it may perturb autophagy and cause neurodegeneration. Although sodium para-aminosalicylic (PAS-Na) has been shown to protect the brain from lead-induced toxicity, the mechanisms associated with its efficacy have yet to be fully understood. In this study, we evaluated the efficacy of PAS-Na in attenuating the neurotoxic effects of lead, as well as the specific mechanisms that mediate such protection. Lead exposure resulted in weight loss and injury to the liver and kidney, and PAS-Na had a protective effect against this damage. Both short-term and subchronic lead exposure impaired learning ability, and this effect was reversed by PAS-Na intervention. Lead exposure also perturbed autophagic processes through the modulation of autophagy-related factors. Short-term lead exposure downregulated LC3 and beclin1 and upregulated the expression of p62; subchronic lead exposure upregulated the expression of LC3, beclin1, and P62. It follows that PAS-Na had an antagonistic effect on the activation of the above autophagy-related factors. Overall, our novel findings suggest that PAS-Na can protect the rat cortex from lead-induced toxicity by regulating autophagic processes.
Graphical Abstract
(1) Short-term lead exposure inhibits autophagy, whereas subchronic lead exposure promotes autophagy. (2) PAS-NA ameliorated the abnormal process of lead-induced autophagy, which had a protective effect on the cerebral cortex.
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Funding support was provided by grants from the National Natural Science Foundation of China (NSFC 81773476).
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LLW: conceptualization, investigation, formal analysis, writing original draft, and writing—review and editing. XJZ: investigation, methodology, formal analysis, and data curation. YYF and YL: revision and polishing of the paper. YSZ, CLG, and JJL: investigation. SYO: investigation and supervision. MA: revision and editing. YMJ: supervision, project administration, and funding acquisition.
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Wang, Ll., Zhu, Xj., Fang, Yy. et al. Sodium Para-Aminosalicylic Acid Modulates Autophagy to Lessen Lead-Induced Neurodegeneration in Rat Cortex. Neurotox Res 41, 1–15 (2023). https://doi.org/10.1007/s12640-022-00615-2
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DOI: https://doi.org/10.1007/s12640-022-00615-2