In vitro and in vivo roles of 3H-1,2-dithiole-3-thione in lipopolysaccharide-induced toxicity and inflammatory injury

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Gabriella M. Gaje (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Zhenquan Jia

Abstract: Lipopolysaccharide (LPS) is a bacterial endotoxin known for being critical in triggering septic shock. It is widely used for studies to understand systemic inflammation that mimics the inflammatory storm of human sepsis patients. 3H-1,2-dithiole-3-thione (D3T) is a common dithiolethione that works as an anti-inflammatory agent in cancers and other inflammatory diseases. However, it is unknown whether D3T can reduce the LPS-induced expression of inflammatory and oxidative stress responses. This study aimed to examine the effect of D3T on LPS-induced expressions of anti-oxidative and anti-inflammatory genes in vivo and in vitro. In vivo mice trials demonstrated that the administration of LPS showed a significant increase in expression of two key proinflammatory genes interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP-1) in liver tissues. D3T significantly reduced the LPS-induced gene expression of MCP-1 and IL-6, in mouse kidney tissue. Similarly, D3T mitigated the LPS-induced gene expression of MCP-1 in mouse liver tissue. Mouse liver tissue treated with D3T showed significant increases in the antioxidant gene expression of GCLM and HO-1. The results indicate that D3T has an inflammatory effect in vivo. For the in vitro portion of the study, 100 µM D3T was able to significantly increase the gene expression of HO-1 and GCLC in THP-1 cells. However, the high concentration of D3T also induced the proinflammatory gene expression of IL-8 in THP-1 cells. D3T at this concentration was not effective in mediating the expression of LPS-induced cytotoxicity or expression of proinflammatory cytokines. This is likely due to the increase of IL-6 by D3T alone. D3T displayed anti-inflammatory properties in vivo, but further studies are needed to explore the effects of D3T in low doses against pro-inflammatory gene expression in THP-1 cells and other cell lines induced by LPS. In conclusion, the results of the current study could contribute to D3T as a potential therapeutic agent to reducing the inflammatory responses caused by the LPS endotoxin in vivo. [This abstract may have been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]

Additional Information

Language: English
Date: 2021
Lipopolysaccharide, Sepsis, 3H-1,2-dithiole-3-thione (D3T), In vivo, In vitro
Endotoxins $x Pathophysiology

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