Tetrahydrocurcumin attenuates phase I metabolizing enzyme-triggered oxidative stress in mice fed a high-fat and high-fructose diet

Abstract

© 2019 Elsevier Ltd Excessive consumption of a fat- and/or fructose-rich hypercaloric diet leads to metabolic syndromes. This study aimed to investigate the hepatoprotective effects of tetrahydrocurcumin (THC), an anti-oxidant metabolite of curcumin, in a hypercaloric diet-induced oxidative stress mouse model. Male ICR mice were fed a high-fat and high-fructose diet (HFFD) containing hydrogenated soybean oil (44.1% saturated fat and 0.2% trans-fatty acids) and a 20% fructose solution for 8 weeks. The HFFD induced hepatic injury through cytochrome P450 (CYP450)-induced oxidative stress, increased glucose tolerance, and increased CYP450 expression. THC attenuated oxidative stress in the HFFD mice by decreasing glucose tolerance, alanine aminotransferase and aspartate aminotransferase levels. In addition, THC suppressed HFFD-induced NADPH-CYP450 reductase activity, restored expression of anti-oxidative stress response related genes, and reduced ROS production by CYP2E1 and CYP3A11. Thus, THC is an excellent candidate for protection against HFFD-induced liver injury related to phase I biotransformation and anti-oxidation pathway.