Ethyl pyruvate supplemented in drinking water ameliorates experimental nonalcoholic steatohepatitis

Inflammation and oxidative stress play a significant role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Ethyl pyruvate (EP) is a novel anti-inflammatory agent and a potent reactive oxygen species (ROS) scavenger. Therefore, EP supplemented in drinking water may alleviate experimental NASH in this study (even though 0.3% of EP cannot attenuate the simple non-aggressive fatty liver). The methionine-choline-deficient (MCD) diet was given to the C57BL/6 male mice for 3 weeks to induce NASH. The NASH animals were randomized into 3 treatment groups: animals in the MCD alone group were treated with normal drinking water alone; animals in the delayed EP group were given 3% (v/v) of EP supplemented in normal drinking water, the treatment started 10 days after MCD diet feeding; animals in the early EP therapy group were treated the same as the delayed EP group except that EP treatment started the same day when MCD diet was given; the control mice were fed with normal chow and treated with normal drinking water (n = 10 for each group). Compared to MCD group with normal drinking water, early EP treatment significantly decreased serum ALT and improved NASH histopathology; delayed EP therapy only attenuated NASH in 50% (5/10) of the animals. The beneficial effects were associated with decreased hepatic TNF-a and IL-6 mRNA expression on early 5 days, inhibited NF-kB activation, reduced liver tissue malondialdehyde levels, and decreased intestinal bacterial translocation (BT). In conclusion: EP supplemented in drinking water attenuates experimental NASH.

Automated summary

EP supplementation in drinking water can attenuate experimental NASH, with early treatment showing significant improvement in serum ALT levels and NASH histopathology. Delayed EP therapy only partially alleviated NASH in 50% of the animals.