Sanghuangporus vaninii polysaccharides alleviates the effects of chlorpyrifos exposure on mouse liver: role of the gut- liver axis.

Chlorpyrifos-induced oxidative stress is associated with intestinal barrier damage. Although some studies have suggested that the liver is the main target organ of chlorpyrifos, the underlying mechanisms remain incompletely understood. Initially, we determined the nontoxic effects of Sanghuangporus vaninii polysaccharide (SVP-60) by acute toxicity experiments (2000 mg/kg). In the present study, we investigated to explore the potential mechanism behind the protective effect of SVP-60 against chlorpyrifos-induced hepatotoxicity. The results showed that chlorpyrifos exposure resulted in growth restriction and impaired liver function and intestinal barrier in mice (14 Days). Intervention with SVP-60 modulated the activities of antioxidant system enzymes and decreased the expression of inflammatory factors. SVP-60 effectively protected against chlorpyrifos-induced liver injury by inhibiting oxidative stress injury via Keap1/Nrf2 signaling pathway and improving inflammation. In addition, SVP-60 treatment (80 μg/mL) reduced the presence of inflammatory factors TNF-α and IL-6 in HepG2 cells, decreasing TNF-α secretion from 412 mg/mL to 317 mg/mL and IL-6 secretion from 61 mg/mL to 34 mg/mL, and enhanced the activities of antioxidant enzymes SOD and GSH-Px. At the same time, the activities of antioxidant enzymes SOD and GSH-Px were enhanced, the activity of SOD increased from 15 U/mg prot to 27 U/mg prot, and the activity of GSH-Px increased from 378 U/mg prot to 429 U/mg prot, and the mRNA expression of Nrf2/Keap1 signaling pathway was regulated, and the mRNA expression of Nrf2 was up-regulated by 2.9 times, and the mRNA expression of Keap1 was down-regulated by 1.7 times. Meanwhile, SVP-60 attenuated the chlorpyrifos-induced intestinal barrier damage and intestinal permeability in mice, and the plasma endotoxin (LPS) level in the index of intestinal permeability was reduced from 689EU/mL to 465 EU/mL, which in turn reduced the secondary damage to the liver caused by LPS leakage. These findings establish a strong correlation between gut and liver injury indicators, highlighting the potential of SVP-60 to prevent and treat chlorpyrifos-induced liver injury by modulating the gut-hepatic axis. The aim of this study was to investigate the specific mechanism by which SVP-60 alleviates CPF-induced liver injury by modulating the gut-liver axis, focusing on its dual protective effects of anti-oxidative stress, inhibition of inflammatory pathways and repair of gut barrier function. Unlike the existing studies that only focused on the direct toxicity of chlorpyrifos to the liver, this study reveals for the first time the trans-organ regulatory mechanism by which SVP-60 indirectly mitigates hepatic injury through the repair of the intestinal barrier.