Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water

Guanghong Yang, Zhiwei Zhou, Yanli Cen, Xiaolin Gui, Qibing Zeng, Yunxia Ao, Qian Li, Shiran Wang, Jun Li, Aihua Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and posttranscriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.

Original languageEnglish (US)
Pages (from-to)4719-4733
Number of pages15
JournalDrug Design, Development and Therapy
Volume9
DOIs
StatePublished - Aug 18 2015
Externally publishedYes

Keywords

  • Fas/FasL pathway
  • Liver injury
  • Mitochondrial pathway

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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