Flavonoid luteolin supplementation inhibits diethylnitrosamine‐initiated alcohol‐promoted hepatic inflammation and precancerous lesions in mice (829.7)

Abstract

Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against chronic diseases. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen (diethylnitrosamine [DEN])‐initiated alcohol‐promoted pre‐neoplastic liver lesion mouse model. C57BL/6 mice were injected with DEN (i.p. 25 mg/kg of body weigth [BW]) at 14 days of age. At 8 weeks of age mice were group pair‐fed with Lieber‐DeCarli liquid control diet or alcoholic diet (EtOH diet, 27% total energy from ethanol) and supplemented with a dose of 30 mg luteolin/kg BW/day for a treatment period of 21 days. Results show a significant induction in the incidence and multiplicity of basophilic and eosinophilic foci, markers of pre‐neoplastic liver lesions, in DEN‐injected mice fed EtOH diet. The presence of pre‐neoplastic lesions was significantly correlated with the induction of steatosis and inflammatory foci in these mice. Supplementation with luteolin inhibited the presence of pre‐neoplastic liver lesions in DEN‐injected mice fed EtOH diet. Dietary luteolin significantly reduced the severity of hepatic inflammatory foci with an associated non‐significant reduction in expression of hepatic inflammatory cytokines TNF‐α, IL‐6 and IL‐1β. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1), however, luteolin supplementation significantly reversed alcohol‐reduced SIRT1 activity assessed by the ratio of acetylated and total FoXO1. The study demonstrated that luteolin prevents EtOH diet‐promoted hepatic inflammation and pre‐neoplastic lesion, potentially mediated by SIRT1‐FoxO1 signaling pathway. Grant Funding Source: USDA/ARS grant 1950‐51000‐074S