{Reference Type}: Journal Article
{Title}: 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside alleviated the acute hepatotoxicity and DNA damage in diethylnitrosamine-contaminated mice.
{Author}: Yu W;Zhao J;Li W;Zheng Y;Zhu J;Liu J;Liu R;Wang Z;Wang X;Hai C;
{Journal}: Life Sci
{Volume}: 243
{Issue}: 0
{Year}: Feb 2020 15
{Factor}: 6.78
{DOI}: 10.1016/j.lfs.2020.117274
{Abstract}: <B>OBJECTIVE: </B>2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) is the key bioactive ingredient extracted from Polygonum multiflorum Thumb. Pharmacological studies suggest that it exerts numerous biological effects, including anti-oxidant, anti-aging, and anti-inflammation. This study aimed at investigating the effect of TSG on diethylnitrosamine (DEN)-induced acute hepatotoxicity and DNA damage.<BR><B>METHODS: </B>Fifty male C57BL/6 mice were randomly divided into 5 groups (n = 10 each): control, DEN, DEN+TSG (low), DEN+TSG (high) and TSG (high) groups. DEN (100 mg/kg) was injected intraperitoneally (i.p.) alone or with TSG (30 or 60 mg/kg, i.p.) for 5 consecutive days.<BR><B>RESULTS: </B>TSG inhibited liver injury and inflammatory cell infiltration in DEN-treated mice. It also attenuated DEN-induced accumulation of reactive oxygen species (ROS), proinflammatory cytokines, and DNA damage. Moreover, TSG promoted the expression of nuclear erythroid 2-related factor 2 (Nrf2) target antioxidant genes by enhancing Nrf2 protein phosphorylation and nuclear translocation. As major phase I detoxification enzymes, cytochrome P450 family 2 subfamily E member 1 (CYP2E1) and cytochrome P450 1 subfamily A member 1 (CYP1A1) are responsible for the metabolic activation of DEN. We found that TSG administration inhibited CYP2E1 and CYP1A1 induction in DEN-treated mice.<BR><B>CONCLUSIONS: </B>These results indicate that TSG can alleviate DEN-induced acute hepatotoxicity by modulating the Nrf2-related antioxidant system and metabolic activation of DEN. Therefore, TSG might be a promising medication for DEN-induced liver injury treatment.