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Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O2•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.

The outcome score is a simple clinical grading scale that allows risk stratification of HD patients presenting with ICH. This scale could be used to design treatment protocols and clinical research studies of ICH in HD patients.

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Background and Purpose-Increased thrombin activity is an essential component of hemostatic reactions. This study elucidates how various hypoxic interventions impact endogenous thrombin generation (TG) after treatment with/without lipophilic antioxidant vitamin E. Methods-Twenty-four healthy sedentary men were randomly assigned to vitamin E (nϭ12) and placebo (nϭ12) groups.These subjects were randomly exposed to 12% (severe hypoxia), 15% (moderate hypoxia), 18% (light hypoxia), and 21% (normoxia) O 2 for 2 hours in a normobaric hypoxia chamber. A novel calibrated, automated thrombinography approach was used to measure TG in plasma. Results-In the placebo group, severe hypoxia enhanced plasma FVIII level/activity and TG, which was accompanied by increased urinary 15-F2t-8-isoprostane level and decreased plasma total antioxidant content and superoxide dismutase activity. However, depletion of FVIII by incubation with anti-FVIII antibodies in plasma suppressed enhancement of TG by severe hypoxia. After administration of 1000 IU vitamin E, severe hypoxia did not significantly alter urinary 15-F 2t -8-isoprostane level and plasma total antioxidant content, superoxide dismutase activity, FVIII level/activity, or TG. Moreover, redox status, FVIII level/activity, and TG were constant in response to moderate hypoxia, light hypoxia, and normoxia in the placebo and vitamin E groups. Conclusion-We conclude that severe hypoxia promotes FVIII-dependent TG, likely by elevating oxidative stress; this

HLE, a human hepatocellular carcinoma cell line was transiently transfected with normal human MnSOD and MnSOD without a mitochondrial targeting signal (MTS). Mitochondrial reactive oxygen species (ROS), lipid peroxidation and apoptosis were examined as a function of time following 18.8 Gy X-ray irradiation. Our results showed that the level of mitochondrial ROS increased and reached a maximum level 2 hours after X-ray irradiation. Authentic MnSOD, but not MnSOD lacking MTS, protected against mitochondrial ROS, lipid peroxidation and apoptosis. In addition, the levels of mitochondrial ROS were consistently found to always correlate with the levels of authentic MnSOD in mitochondria. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by X-ray irradiation and that mitochondria are the critical sites of X-ray-induced cellular oxidative injuries.

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