Chicken meat hydrolysate improves acetaminophen-induced liver injury by alleviating oxidative stress via modulation in Keap1/Nrf2/HO-1 signaling in BALB/c mice

Abstract

Acetaminophen (APAP)-induced hepatotoxicity is a major cause of acute liver injury, primarily due to excessive oxidative stress and inflammation. Chicken meat hydrolysate (CMH) is recognized for their diverse bioactivities, including potent antioxidant and anti-inflammatory properties, making them potential candidates for hepatoprotection. This in vivo study investigates the hepatoprotective potential and underlying mechanisms of CMH against APAP-induced liver injury in BALB/c mice. Enzymatically hydrolyzed CMH was administered via oral gavage at low (50 mg/kg/day) and high (200 mg/kg/day) doses, carnosine (50 mg/kg/day) as a reference standard, for seven consecutive days. On the eighth day, all groups except the Naïve group received APAP (300 mg/kg, i. p.), and mice were sacrificed 24 h later for further evaluation. Our findings demonstrate that one-week pre-treatment with CMH effectively preserved liver morphology, reduced serum liver injury markers including aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and mitigated histopathological alterations. Furthermore, it suppressed inflammatory proteins and cytokine expression, including C-reactive protein, interleukin-6, and monocyte chemoattractant protein-1, while downregulating hepatic 4-hydroxynonenal levels, a marker of lipid peroxidation. Mechanistically, CMH enhanced antioxidant defenses by activating Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and preventing Keap1-mediated Nrf2 degradation. This resulted in increased levels of key antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, as well as intracellular glutathione, promoting hepatic redox balance. Analysis of amino acids and their derivatives revealed high levels of anserine, taurine, and carnosine, supporting their antioxidant and anti-inflammatory roles. Collectively, our results highlight the hepatoprotective effects of CMH against APAP-induced liver injury, supporting its potential as a functional food ingredient for liver health and mitigating APAP-induced acute liver injury.