Paraquat disrupts the anti-inflammatory action of cortisol in human macrophages in vitro: therapeutic implications for paraquat intoxications

Gesiele Verssimo, Aalt Bast, Antje R. Weseler*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

The herbicide paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride) has been banned in Europe since 2007 due to its high toxicity in humans. However, it is still widely used in Middle/ South America and in Asia where it is annually associated with a high incidence of unintentional and intentional poisoning. Human macrophage-like cell lines were used to shed more light on the inflammatory response elicited by paraquat. Paraquat (3-1000 mu M) reduced cell viability in a dose-and time-dependent manner. Exposure to 50 or 200 mu M paraquat for 24 h elevated the release of interleukin 8 and gene expression of tumor necrosis factor-alpha. Expression of the 11 beta-hydroxysteroid dehydrogenase 1 gene tended to increase, while cellular glutathione concentrations decreased. The anti-inflammatory effect of cortisol was significantly disrupted. The paraquat-induced cortisol resistance could not be prevented by N-acetyl-L-cysteine. However, a polyphenolic extract of grape seeds consisting of monomeric and oligomeric flavan-3-ols (MOF) reduced paraquat-induced inflammation in the presence of cortisol to baseline. In conclusion, the results suggest that an impaired cortisol response may contribute to paraquat-mediated inflammation. Agents with pleiotropic cellular and subcellular effects on redox regulation and inflammation, such as plant-derived polyphenols, may be an effective add-on to the therapy of paraquat intoxications with glucocorticoids.

Original languageEnglish
Pages (from-to)232-241
Number of pages10
JournalToxicology Research
Volume6
Issue number2
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • OBSTRUCTIVE PULMONARY-DISEASE
  • INDUCED OXIDATIVE STRESS
  • ACUTE LUNG INJURY
  • KAPPA-B
  • GLUCOCORTICOID RESISTANCE
  • CORTICOSTEROID RESISTANCE
  • INDUCED NEUROTOXICITY
  • TRANSCRIPTION FACTOR
  • HERBICIDE PARAQUAT
  • NADPH OXIDASE

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