Oxidized casein impairs antioxidant defense system and induces hepatic and renal injury in mice

Abstract

Scope: Oxidized protein products (OPPs) can be easily found in meat and milk during processing and storage. Evidence supports that accumulation of endogenous OPPs plays a negative role in physiological metabolism. However, the impacts of dietary OPPs and the mechanisms have not been elucidated yet. The present study evaluated whether oral oxidized casein would destruct the antioxidant defense system and cause potential oxidized injury in mice liver and kidney.

Methods and results: We performed oxidized casein (modified respectively by H2O2-Cu and HClO) feeding experiments using KM mice (20-22 g). A 10-weeks feeding of oxidized casein as basal protein caused oxidative stress by increasing protein carbonylation (PC), advanced oxidation protein products (AOPPs), dityrosine (Dityr), lipid peroxidation and ROS levels in mice liver, kidney and blood (P<0.05). In mice liver and kidney, the mRNA expression of Nrf2, γ-GCS, HO-1, GPX-3, and GPX-4 up-regulated, the protein level of Nrf2 in nucleus increased. However, activities of anti-oxidant enzymes (CAT, SOD, and GPX) decreased (P<0.05). Moreover, histopathological examination displayed the formation of fibrous septa in mice liver and kidney after oxidized casein feeding.

Conclusion: Oxidized casein impairs antioxidant defense system and induces hepatic and renal fibrosis.

Keywords: AOPPs; ARE; Dityr; ET-1; Fibrosis; H–E; MDA; Nrf2; OPPs; Oxidative stress; Oxidized casein; PC; Pox; Protein oxidation; ROS; TGF-β1; advanced oxidation protein products; antioxidant responsive element; dityrosine; endothelin-1; hematoxylin and eosin; malondialdehyde; nuclear factor erythroid 2-related factor; oxidized protein products; protein carbonyl; protein oxidation; reduced oxygen species; transforming growth factor-β1.