Correlation between 3-MCPD-induced organ toxicity and oxidative stress response in male mice. (February 2020)

• Record Type: Journal Article
• Authors: Schultrich, Katharina; Henderson, Colin J.; Braeuning, Albert; Buhrke, Thorsten
• Is Part Of: Food and chemical toxicology. Volume 136(2020)
• Publication Date: 2020-02
• Subjects: 3-MCPD -- Organ toxicity -- Oxidative stress -- Hmox1 activation; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.110957
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Highlights: The transgenic HOTT reporter mouse was employed to examine 3-MCPD-mediated induction of oxidative stress. 3-MCPD induces oxidative stress in mouse kidney, testes and brain. 3-MCPD leads to the irreversible oxidation of the redox sensor protein DJ-1. 3-MCPD does not severely affect Nrf2-dependent gene expression in different mouse organs.