What should also exist are enzymes that efficiently safeguard against excess extracellular H 2O 2. While glutathione helps to maintain an appropriate H 2O 2 level, catalase can specifically and efficiently decompose a large amount of H 2O 2 inside the cell 17. As it is mostly synthesized in hepatocytes and its oral bioavailability is poor 13, 14, glutathione would be depleted during high oxidative stress, which occurs in diseases such as cystic fibrosis (CF) 15, 16. Among the key factors that influence the redox state, glutathione chemically and non-specifically reduces ROS inside and outside cells. Thus, H 2O 2, locally produced by tissue cells or released by leukocytes, must be kept under control. However, excess H 2O 2 could generate oxidative stress, causing unwanted tissue injuries and excessive inflammation, as documented in the literature 2– 12. Strongly reactive oxygen species (ROS), including H 2O 2, are produced by our cells and used in many important processes such as triggering inflammation and providing immunity. Inflammation is a mechanism by which our bodies respond to such harmful stimuli as pathogens, injuries or irritants, manifesting as leukocyte infiltration, tissue injuries, and their repairs 1. Thus, this understudied LPO-SCN − system is an essential protective mechanism in vivo. The mutant mice exhibited inflammation and lesions in the cardiovascular, respiratory, digestive or excretory systems, neuropathology, and tumors, with high incidence. To test this hypothesis, we globally deleted the Lpo gene in mice.

Our group previously showed that this system protected cultured human cells from H 2O 2-caused injuries, a basis for the hypothesis that general deficiency of such an antioxidative mechanism would lead to multisystem inflammation and tumors. While its enzymatic mechanism is understood, the actual biological role of the LPO-SCN − system in mammals remains unestablished. SCN − is the only known natural, effective reducing-substrate of LPO humans normally derive SCN − solely from food. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H 2O 2 to H 2O while oxidizing thiocyanate (SCN −) to relatively tissue-innocuous hypothiocyanite (OSCN −). Strongly oxidative H 2O 2 is biologically important, but if uncontrolled, would lead to tissue injuries.

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