2. Academic Validation
  3. Inhibition of soluble epoxide hydrolase reduces paraquat neurotoxicity in rodents

Inhibition of soluble epoxide hydrolase reduces paraquat neurotoxicity in rodents

  • Environ Toxicol Pharmacol. 2023 Jan 20;98:104070. doi: 10.1016/j.etap.2023.104070.
Jogen Atone 1,  Karen Wagner 1,  Shinichiro Koike 2,  Jun Yang 1,  Sung Hee Hwang 1,  Bruce D Hammock 3
Affiliations

Affiliations

  • 1 Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA 95616, USA.
  • 2 Department of Nutrition, University of California Davis, Davis, CA 95616, USA.
  • 3 Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA 95616, USA. Electronic address: bdhammock@ucdavis.edu.
PMID: 36682504 DOI: 10.1016/j.etap.2023.104070
Abstract

Given the paucity of research surrounding the effect of chronic paraquat on striatal neurotoxicity, there is a need for further investigation into the neurotoxic effects of paraquat in mouse striatum. Furthermore, while previous studies have shown that inhibiting soluble Epoxide Hydrolase mitigates MPTP-mediated endoplasmic reticulum stress in mouse striatum, its effect on paraquat toxicity is still unknown. Thus, this study attempts to observe changes in inflammatory and endoplasmic reticulum stress markers in mouse striatum following chronic paraquat administration to determine whether inhibiting soluble Epoxide Hydrolase mitigates paraquat-induced neurotoxicity and whether it can reduce TLR4-mediated inflammation in primary astrocytes and microglia. Our results show that while the pro-inflammatory effect of chronic paraquat is small, there is a significant induction of inflammatory and cellular stress markers, such as COX2 and CHOP, that can be mitigated through a prophylactic administration of a soluble Epoxide Hydrolase Inhibitor.

Keywords

Anti-inflammatory drugs; Paraquat; Parkinson’s disease; Soluble epoxide hydrolase.

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