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

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.
AuthorsKatharina Schultrich, Colin J Henderson, Albert Braeuning, Thorsten Buhrke
JournalFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 136 Pg. 110957 (Feb 2020) ISSN: 1873-6351 [Electronic] England
PMID31712104 (Publication Type: Journal Article)
CopyrightCopyright © 2019 Elsevier Ltd. All rights reserved.
Chemical References
  • Biomarkers
  • alpha-Chlorohydrin
  • PARK7 protein, mouse
  • Protein Deglycase DJ-1
Topics
  • Animals
  • Biomarkers (metabolism)
  • Brain (drug effects, pathology)
  • Kidney (drug effects, pathology)
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oxidative Stress (drug effects)
  • Protein Deglycase DJ-1 (metabolism)
  • Testis (drug effects, pathology)
  • alpha-Chlorohydrin (toxicity)

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