Preventive treatment with sodium para-aminosalicylic acid inhibits manganese-induced apoptosis and inflammation via the MAPK pathway in rat thalamus.

Abstract

Excessive exposure to manganese (Mn) may lead to neurotoxicity, referred to as manganism. In several studies, sodium para-aminosalicylic acid (PAS-Na) has shown efficacy against Mn-induced neurodegeneration by attenuating the neuroinflammatory response. The present study investigated the effect of Mn on inflammation and apoptosis in the rat thalamus, as well as the underlying mechanism of the PAS-Na protective effect. The study consisted of sub-acute (Mn treatment for 4 weeks) and sub-chronic (Mn and PAS-Na treatment for 8 weeks) experiments. In the sub-chronic experiments, pro-inflammatory cytokines, namely tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and cyclooxygenase 2 (COX-2) were significantly increased in the Mn-exposed group compared to the control II. PAS-Na treatment led to a significant reduction in the Mn-induced neuroinflammation by inhibiting IL-1β and COX-2 mRNA expression and reducing IL-1β secretion and JNK/p38 MAPK pathway activity. Furthermore, immunohistochemical analysis showed that the expression of caspase-3 was significantly increased in both the sub-acute and sub-chronic experimental paradigms concomitant with a significant decrease in B-cell lymphoma 2 (Bcl-2) in the thalamus of Mn-treated rats. PAS-Na also decreased the expression levels of several apoptotic markers downstream of the MAPK pathway, including Bcl-2/Bax and caspase-3, while up-regulating anti-apoptotic Bcl-2 proteins. In conclusion, Mn exposure led to inflammation in the rat thalamus concomitant with apoptosis, which was mediated via the MAPK signaling pathway. PAS-Na treatment antagonized effectively Mn-induced neurotoxicity by inhibiting the MAPK activity in the same brain region.

• Authors: Yue Deng, Dongjie Peng, Chun Yang, Lin Zhao, Junyan Li, Lili Lu, Xiaojuan Zhu, Shaojun Li, Michael Aschner, Yueming Jiang
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 46 Issue 1 Pg. 59-68 (Jan 2023) ISSN: 1525-6014 [Electronic] United States
• PMID: 34875954 (Publication Type: Journal Article)

Chemical References

• Manganese
• Aminosalicylic Acid
• Caspase 3
• Cyclooxygenase 2
• Proto-Oncogene Proteins c-bcl-2

Topics

• Rats
• Animals
• Manganese (toxicity)
• Aminosalicylic Acid (toxicity)
• Caspase 3 (metabolism)
• Cyclooxygenase 2
• Manganese Poisoning (pathology)
• Inflammation (chemically induced, drug therapy, prevention & control)
• Thalamus (metabolism, pathology)
• Apoptosis
• Proto-Oncogene Proteins c-bcl-2 (metabolism)