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

Zhuqing Leslie Li; Ling Mo; Guowei Le; Yonghui Shi

doi:10.1016/j.fct.2013.10.039

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

Food Chem Toxicol. 2014 Feb:64:86-93. doi: 10.1016/j.fct.2013.10.039. Epub 2013 Nov 4.

Authors

Zhuqing Leslie Li¹, Ling Mo¹, Guowei Le², Yonghui Shi³

Affiliations

¹ The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
² The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China; The State Key Laboratory of Food Science and Technology, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
³ The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China; The State Key Laboratory of Food Science and Technology, Food Science and Technology, Jiangnan University, Wuxi 214122, China. Electronic address: yhshi2009@126.com.

PMID: 24200855
DOI: 10.1016/j.fct.2013.10.039

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / pharmacology*
Base Sequence
Blotting, Western
Caseins / chemistry
Caseins / pharmacology*
DNA Primers
Enzyme-Linked Immunosorbent Assay
Kidney / drug effects*
Kidney / injuries
Liver / drug effects*
Liver / injuries
Male
Mice
Oxidation-Reduction
Reverse Transcriptase Polymerase Chain Reaction

Substances

Antioxidants
Caseins
DNA Primers