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 - http://www.scopus.com/inward/record.url?scp=85075377716&partnerID=8YFLogxK
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 -