Lentinan alleviates arsenic-induced hepatotoxicity in mice via downregulation of OX40/IL-17A and activation of Nrf2 signaling

Abstract

AbstractBackgroundArsenic, existing ubiquitously in soil, drinking water, or food, is well known to be an environmental pollutants concerned by European Food Safety Authority.Lentinan,a beta-1,6;1,3-glucan extracts fromLentinus edodes, which has the properties of antioxidant and immunomodulation, present study explored the pharmacological effects ofLentinanon arsenic induced hepatotoxicity in mice.MethodsMice experiments were performed by sodium arsenite (SA) treatment orLentinanintervention, then histopathology, ELISA, Flow Cytometry, or Western-Blotting were applied to evaluate hepatic injury, oxidative stress, CD4+type 17 helper T (Th17) cells, CD4+CD25+Foxp3+regulatory T cells (Tregs), T cells receptor OX40/CD134, IL-17A, NLRP3, Nrf2, and NQO1.ResultsSA treatment showed hepatic pathological injury and the elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in serum, and induced the increases of malondialdehyde (MDA), Th17 cells, OX40 or IL-17A in liver tissues, which were consistently ameliorated byLentinanintervention. Further, immunoblotting experiments showed thatLentinanintervention downregulated the levels of OX40, IL-17A, and NLRP3 signals, while elevated the levels of anti-oxidative Nrf2, NQO1 signals compared to arsenic treatment group. For Tregs,Lentinanintervention showed no significant difference from SA treatment group.ConclusionLentinanantagonizes SA-induced hepatotoxicity in mice, may be involved in the downregulations of pro-inflammatory OX40 or IL-17A and the activation of anti-oxidative Nrf2, NQO1 signals.