Astragaloside IV: a natural shield against ochratoxin A-induced hepatotoxicity in chicks by targeting the NRF2/NLRP3 signaling pathway.

Abstract

Ochratoxin A (OTA) is a prevalent contaminant in feed and poses a serious threat to the poultry industry and public health. The liver is the primary target of OTA, and oxidative stress alongside consequent inflammation, is considered the main contributor to OTA-induced liver damage. Astragaloside IV (AS-IV), a key constituent of the traditional Chinese medicinal herb Astragalus membranaceus, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, immunoregulatory, and organ-protective effects. However, whether AS-IV can ameliorate OTA-induced liver damage remains uncertain. In the current investigation, we investigated the effect of AS-IV on OTA-induced liver damage in chicks and elucidated the underlying mechanisms. The results revealed that AS-IV inhibited OTA-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP) activities. Additionally, AS-IV reversed the OTA-induced decrease in glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities, as well as the increase in malondialdehyde (MDA) content (P < 0.05). The results demonstrated that AS-IV is capable of mitigating mitochondrial damage and reducing the elevation of reactive oxygen species (ROS) in the chicken liver cell line LMH induced by OTA. Moreover, AS-IV was discovered to reverse the OTA-induced decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) expression, and the increase in Kelch-like ECH-associated protein 1(Keap1) expression. Meanwhile, AS-IV also counteracted OTA-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome expression. Taken together, our findings suggested that AS-IV ameliorated OTA-induced hepatotoxicity in chicks by regulating the Nrf2 and NLRP3 signaling pathways.