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

Abstract

Background Arsenic, 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 from Lentinus edodes, which has the properties of antioxidant and immunomodulation, present study explored the pharmacological effects of Lentinan on arsenic induced hepatotoxicity in mice. Methods Mice experiments were performed by sodium arsenite (SA) treatment or Lentinan intervention, 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. Results SA 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 by Lentinan intervention. Further, immunoblotting experiments showed that Lentinan intervention 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, Lentinan intervention showed no significant difference from SA treatment group. Conclusion Lentinan antagonizes 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.

Research Progress of Polysaccharide-Gold Nanocomplexes in Drug Delivery

“…When oxidative stress occurs in the human body, Nrf2 is released from Keap1, enters the nucleus, and interacts with the antioxidant response element (ARE) [ 59 ]. Lentinan (LNT) activated the Nrf2 pathway and inhibited hepatocyte oxidative stress [ 60 ]. Polysaccharides can induce the expression of antioxidant genes or proteins and improve antioxidant effects through the Nrf2/ARE pathway.…”

Lentinan progress in inflammatory diseases and tumor diseases

“…OX40, named CD134 or tumor necrosis factor receptor superfamily member 4 (TNFRSF4), is defined as a biomarker of T cell activation capable of increasing pro-inflammatory cytokines [28]. The latest study found that LNT can downregulate OX40/IL-17A signaling and activate nuclear factor erythroid 2 related factor (Nrf2), an important factor in oxidative stress [29].…”

Nano-curcumin ameliorates arsenic induced hepatotoxicity in female rats

“…It was demonstrated that ursodeoxycholic acid expresses protective effects against arsenic induced hepatotoxicity through Nrf2 (nuclear factor erythroid 2 -related factor 2) signalling pathway (Li et al, 2020). Recently, pharmacological effects of lentinan, αβ -1,6;1,3 glucan extract from Lentinus edodes which has antioxidant and immune-modulating properties, have been studied in mice (Yang et al, 2022).…”