Camel whey protein alleviates heat stress-induced liver injury by activating the Nrf2/HO-1 signaling pathway and inhibiting HMGB1 release

This study aimed to investigate the mechanism by which camel whey protein (CWP) inhibits the release of high-mobility group box 1 (HMGB1) in heat stress (HS)-stimulated rat liver. Administration of CWP by gavage prior to HS inhibited the cytoplasmic translocation of HMGB1 and consequently reduced the inflammatory response in the rat liver, and downregulated the levels of the NLR pyrin domain containing 3 (NLRP3) inflammasome, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. The use of N-acetyl-L-cysteine (NAC), an inhibitor of reactive oxygen species (ROS) production, indicated that this downregulation effect may be attributed to the antioxidant activity of CWP. We observed that CWP enhanced nuclear factor erythroid 2-related factor (Nrf)2 and heme-oxygenase (HO)-1 expression, which inhibited ROS production, nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity, and malondialdehyde (MDA) levels, and increased superoxide dismutase 1 (SOD1) activity and reduced glutathione (GSH) content in the HS-treated liver, ultimately increasing the total antioxidant capacity (TAC) in the liver. Administration of Nrf2 or HO-1 inhibitors before HS abolished the protective effects of CWP against oxidative damage in the liver of HS-treated rats, accompanied by increased levels of HMGB1 in the cytoplasm and IL-1β and TNF-α in the serum. In conclusion, our study demonstrated that CWP enhanced the TAC of the rat liver after HS by activating Nrf2/HO-1 signaling, which in turn reduced HMGB1 release from hepatocytes and the subsequent inflammatory response and damage. Furthermore, the combination of CWP and NAC abolished the adverse effects of HS in the rat liver. Therefore, dietary CWP could be an effective adjuvant treatment for HS-induced liver damage.