Glutathione Reduction of Patulin-Evoked Cytotoxicity in HEK293 Cells by the Prevention of Oxidative Damage and the Mitochondrial Apoptotic Pathway

J Agric Food Chem. 2018 Jul 25;66(29):7775-7785. doi: 10.1021/acs.jafc.8b01212. Epub 2018 Jul 10.

Abstract

Patulin (PAT) is a mycotoxin frequently detected in moldy fruits and fruit products. This study investigated the protective role of glutathione (GSH), an antioxidant agent, against PAT-induced cytotoxicity and its potential mechanisms in HEK293 cells. The obtained results showed that the addition of GSH significantly increased cell viability and decreased apoptosis induced by PAT. Additionally, GSH decreased intracellular ROS and mitochondrial ROS overproduction, suppressed the decline of the mitochondrial membrane potential, and maintained cellular ATP contents. GSH prevented the impairment of mitochondrial oxidative-phosphorylation system and, especially, enhanced the mRNA and protein levels of electron-transport-chain complex III (UQCRC2) and complex V (ATP5, ATP6 and ATP8). Furthermore, GSH increased endogenous GSH contents; enhanced the antioxidant-enzyme activities of SOD, CAT, GR, and GPx; and modulated oxidative damage. These results suggest that GSH reduces PAT-induced cytotoxicity via inhibition of oxidative damage and the mitochondrial apoptotic pathway in HEK293 cells.

Keywords: HEK293 cell; apoptosis; glutathione (GSH); oxidative stress; patulin (PAT).

MeSH terms

  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Electron Transport Complex III / genetics
  • Electron Transport Complex III / metabolism
  • Glutathione / metabolism*
  • HEK293 Cells
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mycotoxins / toxicity*
  • Oxidative Stress / drug effects*
  • Patulin / toxicity*

Substances

  • Mycotoxins
  • Patulin
  • Electron Transport Complex III
  • Glutathione