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Diallyl Disulfide Attenuates STAT3 and NF-κB Pathway Through PPAR-γ Activation in Cerulein-Induced Acute Pancreatitis and Associated Lung Injury in Mice

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Abstract

We have previously shown that diallyl disulfide (DADS) protects mice against cerulein-induced acute pancreatitis (AP) and associated lung injury. However, the molecular mechanisms underlying its effect and the components involved have not been studied. We hypothesized that DADS may reduce TNF-α, CSE expression, H2S production, STAT3, and NF-κB activation and induce SOCS3 expression through peroxisome proliferator-activated receptor γ (PPAR-γ) pathway in cerulein-induced mice. Male Swiss mice were treated with hourly intraperitoneal injections of cerulein (50 µg/kg) for 6 h. Diallyl disulfide (200 μg/kg) was administered in the presence or absence of PPAR-γ antagonist GW9662 (0.3 mg/kg) (i.p) 1 h after the induction of AP. Our findings revealed that DADS blocked TNF-α, CSE expression, H2S production, and STAT3, and NF-κB activation was reversed by GW9662. Furthermore, GW9662 abrogated DADS-induced SOCS3 expression. The results show for the first that DADS-induced anti-inflammatory effect in acute pancreatitis is regulated through PPAR-γ.

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Acknowledgements

This work was supported by Seed Grant from the Vellore Institute of Technology and Technical supported by the Technical Business Incubator of Vellore Institute of Technology, Vellore, Tamil Nadu, India.

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  1. School of Biological Science, Vellore Institute of Technology, Vellore, Tamil Nadu, India

    Mathan Kumar Marimuthu, Anbalagan Moorthy & Tamizhselvi Ramasamy

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Contributions

Category 1 Conception and design of study: Dr. R. Tamizhselvi, Acquisition of data: M. Mathan Kumar, Analysis and or interpretation of data: M. Mathan Kumar, Dr. M. Anbalagan, Dr. R. Tamizhselvi, Category 2, Drafting the manuscript: M. Mathan Kumar, Dr. R. Tamizhselvi, Revising the manuscript critically for important intellectual content: Dr. R. Tamizhselvi, Category 3, Approval of the version of the manuscript to be published: M. Mathan Kumar, Dr. R. Tamizhselvi.

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Correspondence to Tamizhselvi Ramasamy.

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Marimuthu, M.K., Moorthy, A. & Ramasamy, T. Diallyl Disulfide Attenuates STAT3 and NF-κB Pathway Through PPAR-γ Activation in Cerulein-Induced Acute Pancreatitis and Associated Lung Injury in Mice. Inflammation 45, 45–58 (2022). https://doi.org/10.1007/s10753-021-01527-7

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