All 16 male and 23 female wild-type mice remained whereas 28 out of 45 male and 40 out 53 female mutant mice remained. ( c) Percentage of wild-type (black line) and mutant (magenta curve) mice remaining at one year of age. ( b) Two competing MPO-catalyzed reactions: oxidation of SCN в€’ to OSCN в€’ and Cl в€’ to OCl в€’. ( a) LPO-catalyzed oxidation reaction of SCN в€’ by H 2O 2 to OSCN в€’. Reaction schemes, survival curves, body weight and incidents of histological findings in major organs of Lpo del cohort. While being a helpful bactericide, the resulting OSCN в€’ is relatively tissue innocuous 21, 23, 31, 33, 35. By subjecting itself to oxidation, SCN в€’ can prevent a harmful accumulation of ROS, such as H 2O 2 and hypochlorite (OCl в€’), and thus ROS-induced cytotoxicity 18. Its substrate SCN в€’ flows out of cells via anion channels, such as the channel whose genetic defects cause CF 26вЂ“ 28, yielding 400В ОјM SCN в€’ in such secretions as the airway fluid 23, 29вЂ“ 34. LPO has since been found in the secretions of many organs such as lungs, intestines, and breasts 23вЂ“ 25. As outlined below, on the backdrop of enzymatic studies on haloperoxidases, a cell-biological research from our laboratory, which was initiated to understand inflammatory pathology in CF, leads to the proposal that lactoperoxidase (LPO) is a such protective enzyme 18.ДЇour decades ago, LPO was shown to catalyze a redox reaction where H 2O 2 is reduced to H 2O while SCN в€’ is oxidized to hypothiocyanite (OSCN в€’) 19вЂ“ 22 (Fig.

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 2вЂ“ 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 в€’ 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 в€’ system in mammals remains unestablished. SCN в€’ is the only known natural, effective reducing-substrate of LPO humans normally derive SCN в€’ solely from food. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H 2O 2 to H 2O while oxidizing thiocyanate (SCN в€’) to relatively tissue-innocuous hypothiocyanite (OSCN в€’). Strongly oxidative H 2O 2 is biologically important, but if uncontrolled, would lead to tissue injuries.

Chem c3000 supplemental chemicals