Bilirubin, the end product of heme catabolism in mammals, is generally regarded as a potentially cytotoxic, lipid-soluble waste product that needs to be excreted. However, it is here that bilirubin, at micromolar concentrations in vitro, efficiently scavenges peroxyl radicals generated chemically in either homogeneous solution or multilamellar liposomes. The antioxidant activity of bilirubin increases as the experimental concentration of oxygen is decreased from 20% (that of normal air) to 2% (physiologically relevant concentration). Furthermore, under 2% oxygen, in liposomes, bilirubin suppresses the oxidation more than alpha-tocopherol, which is regarded as the best antioxidant of lipid peroxidation. The data support the idea of a "beneficial" role for bilirubin as a physiological, chain-breaking antioxidant.

Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radicaltrapping activity were also electrochemically active as reducing agents in cyclic voltammetric measurements. Furthermore, carnosine inhibited the oxidative hydroxylation of deoxyguanosine induced by ascorbic acid and copper ions. Other roles of carnosine, such as chelation of metal ions, quenching of singlet oxygen, and binding of hydroperoxides, are also discussed. The data suggest a role for these histidine-related compounds as endogenous antioxidants in brain and muscle.One of the processes involved in the adaptation of organisms to live in an aerobic atmosphere was the development of mechanisms for defense against damage induced by oxygen and active oxygen species (1). Active oxygen has been suggested as a major cause of cancer, aging, and several diseases (1-6). These reactive compounds can react with DNA, RNA, lipids, and proteins (1-7).Natural defense mechanisms vary from one species to another and within the tissues of the same species. Skeletal muscle and brain are two of the tissues that have the most active oxidative metabolism, yet the concentrations of the antioxidants vitamin E and vitamin C in these tissues are not particularly high (8,9). Carnosine (,B-alanyl-L-histidine) was discovered at the beginning of the century in skeletal muscle (10). Since then, carnosine and related compounds anserine (8-alanyl-3-methyl-L-histidine) and homocarnosine (y-aminobutyryl-Lhistidine) have been reported (11) to be present in the range of 1-20 mM in the skeletal muscles of many vertebrates. There are high levels of carnosine in human muscles (2-20 mM) (11), olfactory epithelium and bulbs (0.3 mM-5 mM) (12)(13)(14)(15), and in other parts of the brain. Homocarnosine is present in cerebrospinal fluid and brain (2-50 p.M) (12)(13)(14)(15)(16)(17), and anserine is present in the brain (18).Although it is accepted that camosine and its analogues should play some physiological role in muscle and brain, no unified hypothesis exists that can satisfactorily explain their role (18). Carnosine has been postulated to act as a buffer to neutralize lactic acid produced in skeletal muscle that is undergoing anaerobic glycolysis (19 Assay for the Lipid Peroxyl Radical-Trapping Activity. The azo compounds 2,2'-azobis(2,4-dimethylvoleronitrile) (AMVN) and 2,2'-azobis(2-amidinopropane dihydrochloride) (AAPH) (Polyscience, Warrington, PA) were used as free-radical initiators in both homogeneous and liposome systems (30)(31)(32). The rate of peroxyl-radical formation from these initiators is constant at a given temperature and, once produced, can initiate free-radical ch...

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The NF-kappaB family consists of a group of inducible transcription factors which regulate immune and inflammatory responses and protect cells from undergoing apoptosis in response to cellular stress. A number of signal transduction cascades can activate the NF-kappaB pathway to result in the translocation of the NF-kappaB proteins from the cytoplasm to the nucleus where they activate the expression of specific cellular genes. In this review, we discuss cellular genes which are regulated by NF-kappaB and disease states which are associated with constitutive activation of the NF-kappaB pathway. Strategies to prevent prolonged activation of the NF-kappaB pathway are also discussed.

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