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

TY - JOUR

T1 - Correlation between 3-MCPD-induced organ toxicity and oxidative stress response in male mice

AU - Schultrich, Katharina

AU - Henderson, Colin J.

AU - Braeuning, Albert

AU - Buhrke, Thorsten

N1 - This project was funded by the German Federal Institute for Risk Assessment (project 1322-660). The HOTT mouse was developed under European Research Council Advanced Investigator Award number 294533.

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - 3-MCPD

KW - Hmox1 activation

KW - Organ toxicity

KW - Oxidative stress

UR - https://www.scopus.com/pages/publications/85075377716

U2 - 10.1016/j.fct.2019.110957

DO - 10.1016/j.fct.2019.110957

M3 - Article

C2 - 31712104

SN - 0278-6915

VL - 136

SP - 1

EP - 9

JO - Food and Chemical Toxicology

JF - Food and Chemical Toxicology

M1 - 110957

ER -