Correlation between 3-MCPD-induced organ toxicity and oxidative stress response in male mice

Katharina Schultrich, Colin J. Henderson, Albert Braeuning, Thorsten Buhrke (Lead / Corresponding author)

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2 Citations (Scopus)
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Abstract

3-Chloro-1,2-propanediol (3-MCPD) is a food contaminant which has been classified as a non-genotoxic carcinogen (category 2B). Previous studies suggested that oxidative stress might play a role in 3-MCPD toxicity. To elucidate the impact of 3-MCPD-mediated organ toxicity in more detail, transgenic reporter mice were employed which contain a lacZ reporter under the control of the heme oxygenase 1 (Hmox1) promoter which is responsive to oxidative stress. The mice received daily doses of up to 100 mg/kg body weight 3-MCPD per day in a 28-day feeding study. Subsequently, tissue slices from different organs were subjected to X-Gal staining as the readout for lacZ gene expression. A dose-dependent increase of blue stain was observed in mouse kidney that was exclusively visible in the renal cortex but not in the renal medulla. Moreover, blue-stained regions were detected in the basal membrane of the seminiferous tubules in testes and also in specific brain regions (cerebellum, midbrain and pons). Notably, gene expression of a number of Nrf2-dependent target genes except Hmox1 was not severely affected by 3-MCPD. In all three organs, however, the amount of irreversibly oxidized DJ-1 protein, which is a biomarker for oxidative stress, was significantly increased already by low doses of 3-MCPD.

Original languageEnglish
Article number110957
Pages (from-to)1-9
Number of pages9
JournalFood and Chemical Toxicology
Volume136
Early online date8 Nov 2019
DOIs
Publication statusPublished - Feb 2020

Keywords

  • 3-MCPD
  • Hmox1 activation
  • Organ toxicity
  • Oxidative stress

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