title: Vulnerability of brain tissue to inflammatory oxidant, hypochlorous acid.
abstract: CNS inflammation is a sequela of a variety of neuropathological conditions resulting in extensive tissue loss. Inflammation is mediated primarily by phagocytic cells, but the mechanisms of CNS tissue destruction are not fully understood. Hypochlorous acid (HOCl) is by far the most abundant agent generated by phagocytic cells and may be the major mediator of inflammatory tissue damage. However, the effects of HOCl on nervous tissue have not been examined. In this study we used an in vitro model system of rat brain slices to determine neurotoxicity of HOCl. The slices were exposed to HOCl at pathologically relevant doses, and the incorporation of [3H]leucine into proteins and lipids was analyzed in total homogenate, and in particulate fractions obtained by density gradient centrifugation. The results demonstrated that a brief HOCl exposure profoundly suppressed protein biosynthesis in the slices. Also, lipid synthesis was suppressed in nonmyelin particulate fraction. However, lipid synthesis in myelin was significantly stimulated in HOCl-exposed slices indicating that oligodendrocyte response to the oxidant differs from that of other CNS cells. The effects of HOCl could be blocked by coadministration of antioxidants, i.e., N-acetylcystein (NAC), uric acid (UA) and ascorbic acid (AA). The protective potency of the antioxidants was NAC>UA>AA. In conclusion, our study demonstrated that HOCl generated by phagocytic cells during inflammatory episodes has a potential to damage surrounding CNS tissue, and that tissue damage can be prevented by HOCl scavenging with clinically applicable antioxidants.
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University School of Medicine, 4052 HSCN, P.O. Box 9128, Morgantown, WV 26506-9128, USA.
authors.forename: Alicja
authors.initials: A
authors.lastname: Krasowska
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Konat
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006997:Hypochlorous Acid / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D016877:Oxidants / Q000633:toxicity*; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D016877:Oxidants; D006997:Hypochlorous Acid