PMID- 14706870
OWN - NLM
STAT- MEDLINE
DCOM- 20040324
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 997
IP  - 2
DP  - 2004 Feb 6
TI  - Vulnerability of brain tissue to inflammatory oxidant, hypochlorous acid.
PG  - 176-84
AB  - 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.
FAU - Krasowska, Alicja
AU  - Krasowska A
AD  - Department of Neurobiology and Anatomy, West Virginia University School of 
      Medicine, 4052 HSCN, P.O. Box 9128, Morgantown, WV 26506-9128, USA.
FAU - Konat, Gregory W
AU  - Konat GW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antioxidants)
RN  - 0 (Oxidants)
RN  - 712K4CDC10 (Hypochlorous Acid)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology/therapeutic use
MH  - Brain/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hypochlorous Acid/*toxicity
MH  - Inflammation/*chemically induced/metabolism/prevention & control
MH  - Oxidants/*toxicity
MH  - Protein Biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2004/01/07 05:00
MHDA- 2004/03/25 05:00
CRDT- 2004/01/07 05:00
PHST- 2004/01/07 05:00 [pubmed]
PHST- 2004/03/25 05:00 [medline]
PHST- 2004/01/07 05:00 [entrez]
AID - S0006899303039635 [pii]
AID - 10.1016/j.brainres.2003.09.080 [doi]
PST - ppublish
SO  - Brain Res. 2004 Feb 6;997(2):176-84. doi: 10.1016/j.brainres.2003.09.080.