- ( Chen et al.,1998 ) ( Vaughan et al.,1995 ) ( Yamada et al., 1994 ) ( Zamboni et al., 1993 ) - xenobiotics P % ( superoxide ) ( Nohl and Jor

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1 - ( Ischemia-reperfusion I/R ) ( Tsao et al.,1990 ; Wang et al., 1997 ;Pang et al., 1993 ) Atalla et al.,1985 Chiu and Toledo-Pereyra, 1987 Flye and Yu, 1987 Lambotte et al., ( Antioxidants ) -1-

2 - ( Chen et al.,1998 ) ( Vaughan et al.,1995 ) ( Yamada et al., 1994 ) ( Zamboni et al., 1993 ) - xenobiotics P % ( superoxide ) ( Nohl and Jordan, 1986 ) 2 % ( Boveris and Chance,1973 ) -2-

3 ( xanthine oxidase ) ( aldehyde oxidase ) leucoflavins tetrahydropterins hydroquinones ferrodoxins ( Fridovich, 1983,1986 ) C ( Chance et al., 1979 ) Fenton ( proteolytic enzyme ) ( azurophilic granule ) myeloperoxidase ( MPO) ( Mullane et al., 1988 ) MPO ( chloride ) hypochlorous acid ( HOCl ) ( singlet oxygen 1 O 2 ) -3-

4 ( sarcoplasmic reticulum) ( sarcolemma ) ( Grisham et al., 1984 ) ( Moncada et al.,1991; Nathan, 1992 ) peroxynitrite ( ONOO - ) ONOO - ( thio group ) ONOO - ( Radi et al.,1991 ) ( Ischemia reperfusion injury, I/R injury ) 1995 Menger - ( no-reflow ) - ( reflow- paradox ) - ( no-reflow )( Menger et al.,1992 ) ( Cytotoxic mediators ) -4-

5 - ( reflow- paradox )( Menger et al., 1992 ) Menger (homeostasis ) ( necrosis ) ( Grace PA.,1994 ) 1996 Verrier Tsao 2.5 ( oxygen- derived free radical ) -5-

6 ( Bulkley, 1987 ) ( xanthine dehydrogenase xanthine oxidase system ; XDH XO system ) ( Manson et al., 1983 ; Im et al., 1984 ) ( adenosine triphosphate ; ATP ) ( xanthine) ( xanthine dehydrogenase ) ( xanthine dehydrogenase ) ( xanthine dehydrogenase ) xanthine oxidase ( adenosine 5 - monophosphate ) ( hypoxanthine ) ( hypoxanthine ) ( xanthine) (Granger et al., 1983 ; Parks et al., 1983 ) -6-

7 ( Marzella et al., 1988 ) ( Nitric Oxide, NO ) ( endothelin ) ( prostaglandin ) ( Tsao et al.,1990 ; Wang et al., 1997 ;Pang et al., 1993 ) ( permeability ) ( Gute et al., 1998 ) ( Wang et al., 1997 ) ( acute inflammatory responses ) ( adhesion molecules ) ( Talbott et al., 1994 ) selectins integrins immunoglobulin superfamily ( neutrophil ) ( platelets ) - -7-

8 SOD ( superoxide dismutase ) ( Fridovich,1983,1986 ) SOD / SOD / SOD ( Weisiger et al., 1973 ) SOD O H + H 2 O 2 + O 2 ( catalase CAT ) CAT CAT H 2 O 2 2H 2 O + O 2 SOD CAT Atalla et al.,1985 Chiu and Toledo-Pereyra, 1987 Flye and Yu, 1987 Lambotte et al., 1988 Romani et al., 1988 Castillo., 1990 Cho et al., 1990 Nauta et al., 1990 SOD CAT -8-

9 ( Manson et al.,1983 Sagi A et al., ) ( Pyatak et al., 1980 Turrens et al., 1984 ) Allopurinol Allopurinol ( xanthine oxidase ) ( Elion et al., 1966 ) ( superoxide O - 2 ) ( Crowell et al., 1969 ) ( DeWall et al., 1971 ) ( Mes et al., 1980 ) allopurinol ( Vaughan et al., 1995 ) ( xanthine oxidase ) ( adenine nucleotides ) ( Puig et al., 1989 ) ( electron transport chain ) ( Moorhouse et al., 1987 Peterson et al., 1986 ) Rhoden allopurinol Carnosine Carnosine ( -alanyl- L -histidine)

10 dipeptide (striated muscles) mmol/kg wet weight Carnosine homocarnosine ( -butyryl- L-histidine) (olfactory bulb) 10 mmol/ kg wet weight ( Margolis, F. L., 1983) Carnosine (Davey, CL.,1976) (Stvolinsky S.,2000) ( Boldyrev A.,2001) Carnosine anserine (N 1 -methylated derivatives) ophidine (N 3 -methylated derivatives) carcinine (decarboxylated derivative) (Nagai, K. et. al.,1988) ( Kurella, E. et al.,1997) ( Pegova A. et 2000) ( Boldyrev A. et al., 1999 Quinn et al.,1992 Gallant et al.,2000 ) carnosine amyloid peptide fragment ( Bonfanti et al., 1999; Klebanov et al., -10-

11 1998 ) (Alzhemer s disease) cross-linking ROS (reactive oxygen species) glycation protein carbonyl glycoxidation lipoxidation ( Hipkiss et al.,1998; Preston et al.,1998 ) Carnosine amino groups imidazole carboxyl groups glycoxidation CML(N -carboxmethyllysine) pentosidine lipoxidation MDA(malondialdehyde) HNE(4-hydroxy-nonenal) protein carbonyl deoxyribose protein-carbonyl-carnosine carnosinylated protein cross-linking ( Lee et al.,1999; Roberts et al.,1998 ) Mannitol Mannitol (Rudehill et al.,1993) mannitol ( Burke et al.,1981) ( Cote et al.,1979) ( Ouriel et al.,1985) -11-

12 ( Buchbinder et al.,1981) mannitol ( Goldstein et al.,1984) ( Schaff et al.,1981) ( Parks et al.,1983) Narayanan mannitol mannitol / 1967 Strauch Murray ( free-tissue transfers ) 1984 Petry Wortham ( fluorescein) ( Dunn et al.,1992 ) ( epigastric artery and vein ) ( inguinal fat pads ) -12-

13 1997 ( recipient bed ) ( Wang et al., 1997 ) 0 % 26.2 % 20.6 % ( cytokines ) -13-

14 ( target cell ) ( Cain et al., 1999 ) ( primary proinflammatory substrate ) -alpha ( tumor necrosis factor, TNF-α ) -1 beta ( interleukin-1, IL-1β ) ( Meldrum, 1998 Latini et al., 1994 Levine et al., 1990 Torre-Amione et al., 1995 Oral et al., 1995 Ishiyama et al., 1997 Olivetti et al.,1997 ) ( Dinarello, 1990 ) ( Okusawa et al., 1988 ) -alpha ( TNF-α ) -1 beta (IL-1β ) ( Kumar et al., 1996 ) Murray -alpha ( Murray and Freeman, 1995 ) TNF IL-1 ( Dinarello and Charles, 2000 ) -14-

15 T TNF IL-1 ( Yoon et al., 1998 Vigers et al., 1997 Poltorak et al., 1998 ) ( hyperbaric ) ( 1 atmosphere) ( hyperbaric oxygen ; HBO 2 ) ( hyperbaric chamber ) ( mask ) 100 % ( Grim et al., 1990 ) ; 1.4 ( Thom, 1992 ) ( Aitasalo et al., 1998 ; Baykal et al., 1996 ) ( decompression sickness ) ( carbon monoxide poisoning ) ( arterial gas embolism ) ( thermal burns injury ) ( crush injury ) ( acute traumatic injury ) ( compartment syndrome ) ( compromised skin grafts and flaps ) ( problem -15-

16 wounds ) ( refractory osteomyelitis ) ( radiation-induced tissue injury ) mmhg mmhg mmhg 30 mmhg ( Jann,1999) 3 ( 3ATA ) 2280 mmhg 0.3 % 6.84 vol% (N2) -16-

17 ( Kolski et al.,1998 ) (ICAM-1) ( integrin - 2 ) ( xanthine dehydrogenase ) xanthine oxidase ( Nylander et al., 1987 ) ( Thom et al.,1999 ) 1993 Zamboni ( Ellis et al., 1983 ; Kenward et al., 1980 ; Weisemfeld et al., 1990 ) DNA RNA ( Hill et al., 1972 ) 3-17-

18 ( O - 2 H 2 O 2 OH. ) dihydroxyacid dehydrtase ( Kenward et al., 1980 ) valine leucine ( Knighton et al., 1990 ) thiamine nicotinamide adenine dinucleotide ( NAD NADH ) 1995 Tresse aminoglucosides sulfonamides -18-

19 50-58% ( scavengers )

Richard et al., 1980, Kawamura et al., 1990) (neurons) 15% (glia cells) 85% (astrocyte > 80% ) (oligodendrocyte < 5% ) (microglia 12-15% ) (Perry et a

Richard et al., 1980, Kawamura et al., 1990) (neurons) 15% (glia cells) 85% (astrocyte > 80% ) (oligodendrocyte < 5% ) (microglia 12-15% ) (Perry et a ( ) (Nakashima et al., 1995; Davies et al., 1998; Morioka et al., 1993; Gehrmann et al., 1992) (Selman et al., 1980) (barbiturate) (Selman et al., 1980) (steroids) (lysosomal enzyme) (Anderson et al.,