PMID- 36063295 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20240106 IS - 1573-6903 (Electronic) IS - 0364-3190 (Print) IS - 0364-3190 (Linking) VI - 48 IP - 1 DP - 2023 Jan TI - Sodium Para-aminosalicylic Acid Inhibits Lead-Induced Neuroinflammation in Brain Cortex of Rats by Modulating SIRT1/HMGB1/NF-kappaB Pathway. PG - 238-249 LID - 10.1007/s11064-022-03739-1 [doi] AB - Lead (Pb) is considered to be a major environmental pollutant and occupational health hazard worldwide which may lead to neuroinflammation. However, an effective treatment for Pb-induced neuroinflammation remains elusive. The aim of this study was to investigate the mechanisms of Pb-induced neuroinflammation, and the therapeutic effect of sodium para-aminosalicylic acid (PAS-Na, a non-steroidal anti-inflammatory drug) in rat cerebral cortex. The results indicated that Pb exposure induced pathological damage in cerebral cortex, accompanied by increased levels of inflammatory factors tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). Moreover, Pb decreased the expression of silencing information regulator 2 related enzyme 1 (SIRT1) and brain-derived neurotrophic factor (BDNF), and increased the levels of high mobile group box 1 (HMGB1) expression and p65 nuclear factor-kappaB (NF-kappaB) phosphorylation. PAS-Na treatment ameliorated Pb-induced histopathological changes in rat cerebral cortex. Moreover, PAS-Na reduced the Pb-induced increase of TNF-alpha and IL-1beta levels concomitant with a significant increase in SIRT1 and BDNF levels, and a decrease in HMGB1 and the phosphorylation of p65 NF-kappaB expression. Thus, PAS-Na may exert anti-inflammatory effects by mediating the SIRT1/HMGB1/NF-kappaB pathway and BDNF expression. In conclusion, in this novel study PAS-Na was shown to possess an anti-inflammatory effect on cortical neuroinflammation, establishing its efficacy as a potential treatment for Pb exposures. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Zhao, Yue-Song AU - Zhao YS AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. FAU - Li, Jun-Yan AU - Li JY AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. AD - Hengyang Center for Disease Control and Prevention, Hengyang, China. FAU - Li, Zhao-Cong AU - Li ZC AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. FAU - Wang, Lei-Lei AU - Wang LL AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. FAU - Gan, Cui-Liu AU - Gan CL AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. FAU - Chen, Jing AU - Chen J AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. FAU - Jiang, Si-Yang AU - Jiang SY AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. FAU - Aschner, Michael AU - Aschner M AD - Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. FAU - Ou, Shi-Yan AU - Ou SY AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. ayin.ou@163.com. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. ayin.ou@163.com. FAU - Jiang, Yue-Ming AU - Jiang YM AD - Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd., Nanning, 530021, Guangxi, China. ymjianggxmu@163.com. AD - Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. ymjianggxmu@163.com. LA - eng GR - R01 ES007331/ES/NIEHS NIH HHS/United States GR - 81773476/National Natural Science Foundation of China/ PT - Journal Article DEP - 20220905 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (NF-kappa B) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 5B2658E0N2 (Aminosalicylic Acid) RN - 0 (HMGB1 Protein) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9NEZ333N27 (Sodium) RN - EC 3.5.1.- (Sirtuin 1) RN - 2P299V784P (Lead) RN - 0 (Anti-Inflammatory Agents) RN - EC 3.5.1.- (Sirt1 protein, rat) SB - IM MH - Rats MH - Animals MH - NF-kappa B/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - *Aminosalicylic Acid MH - *HMGB1 Protein/metabolism MH - Rats, Sprague-Dawley MH - Tumor Necrosis Factor-alpha/metabolism MH - Neuroinflammatory Diseases MH - Sodium MH - Sirtuin 1/metabolism MH - Lead/toxicity MH - Brain/metabolism MH - Cerebral Cortex/metabolism MH - Anti-Inflammatory Agents PMC - PMC9825627 MID - NIHMS1835773 OTO - NOTNLM OT - BDNF OT - Lead OT - Neuroinflammation OT - PAS-Na OT - SIRT1/HMGB1/NF-kappaB pathway COIS- Competing Interests The authors have no relevant financial or non-financial interests to disclose. EDAT- 2022/09/06 06:00 MHDA- 2023/01/11 06:00 PMCR- 2023/01/08 CRDT- 2022/09/05 11:18 PHST- 2022/05/17 00:00 [received] PHST- 2022/08/25 00:00 [accepted] PHST- 2022/08/19 00:00 [revised] PHST- 2022/09/06 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/09/05 11:18 [entrez] PHST- 2023/01/08 00:00 [pmc-release] AID - 10.1007/s11064-022-03739-1 [pii] AID - 10.1007/s11064-022-03739-1 [doi] PST - ppublish SO - Neurochem Res. 2023 Jan;48(1):238-249. doi: 10.1007/s11064-022-03739-1. Epub 2022 Sep 5.