Nitrite and catalase levels rule oxidative stability and safety properties of milk: a review

This review focuses on recent evidence showing that various types of udder inflammation (mastitis) are associated with increased concentration of NO˙-derived metabolites, nitrite and nitrate, and oxidatively modified organic components under commercial farming and experimental conditions. In milk, NO˙ constantly cycles through: (i) auto oxidation to nitrite; (ii) hydrogen peroxide-dependent conversion of nitrite into NO2˙ by lactoperoxidase; (iii) interaction of NO2˙ with thiyl (RS˙) radicals on proteins formed by NO˙ to generate S-nitrosothiols; and (iv) disintegration of NO˙ from S-nitrosothiols, which completes the cycle. The main mechanism which restrains this cycle is conversion of nitrite to nitrate by catalase in a hydrogen peroxide dependent manner. The main source of hydrogen peroxide in milk derives from the oxidation of secreted hypoxanthine and xanthine by xanthine oxidoreductase. Formation of NO2˙ has an important role in the glandular innate defense system because it has bactericidal effects towards major pathogens that infect the mammary gland. However, increased formation of NO2˙ that occurs during mastitis and extended storage of milk for more than three days, even when kept in cold, dark conditions, induce nitrosative stress on milk organic components. Nitrosative stress in milk is reflected by a marked increase in the concentration of 3-nitrotyrosine, carbonyl and lipid peroxides. Thus, it is possible that current criteria for dairy plants acceptance of milk overlook important information on milk safety for consumption by humans. The literature regarding the presence of nitrite and nitrate in milk under experimental, farm and marketed milk is reviewed and the potential implications discussed. Relevant conclusions to improve safety of milk for human consumption are derived, and the particular importance in applying such recommendations for milk designated for the manufacturing of infant formulas is outlined.