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Titolo:
SUPEROXIDE INHIBITION FOLLOWING DIFFERENT STIMULI OF RESPIRATORY BURST AND METABOLISM OF AMINOSALICYLATES IN NEUTROPHILS
Autore:
ALLGAYER H; RANG S; KLOTZ U; BOHNE P; RETEY J; KRUIS W; GUGLER R;
Indirizzi:
KLINIKUM KARLSRUHE,MED CLIN 1,MOLTKESTR 14 W-7500 KARLSRUHE GERMANY DR MARGARETE FISCHER BOSCH INST CLIN PHARMACOL W-7000 STUTTGART GERMANY PROTESTANT HOSP KOLN KALK COLOGNE GERMANY
Titolo Testata:
Digestive diseases and sciences
fascicolo: 1, volume: 39, anno: 1994,
pagine: 145 - 151
SICI:
0163-2116(1994)39:1<145:SIFDSO>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
INFLAMMATORY BOWEL-DISEASE; 5-AMINOSALICYLIC ACID; ULCERATIVE-COLITIS; SULFASALAZINE; SULPHASALAZINE; ACETYLATION; GENERATION; HYDROXYL; CELLS; FMLP;
Keywords:
SUPEROXIDE RADICALS; INHIBITION; 5-AMINOSALICYLIC ACID; 4-AMINOSALICYLIC ACID; BENZALAZINE; OLSALAZINE; LIPOPOLYSACCHARIDE; N-ACETYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
H. Allgayer et al., "SUPEROXIDE INHIBITION FOLLOWING DIFFERENT STIMULI OF RESPIRATORY BURST AND METABOLISM OF AMINOSALICYLATES IN NEUTROPHILS", Digestive diseases and sciences, 39(1), 1994, pp. 145-151

Abstract

Reactive oxygen species such as superoxide radicals have been proposed to play an important role in the pathogenesis of inflammatory bowel disease. Some of the antiinflammatory actions of aminosalicylates havebeen ascribed to their capability to scavenge superoxide radicals directly or to inhibit its production in stimulated neutrophils. However,as a controversy still exists with regard to the precise mechanisms of inhibition and the metabolism within inflammatory cells, we comparedscavenger properties of 5-aminosalicylic acid, 4-aminosalicylic acid,N-acetyl aminosalicylic acid, olsalazine, and benzalazine in systems with defined superoxide radical generation such as the dimethyl sulfoxide-NaOH and the potassium superoxide system. We also studied possibleinhibition of the superoxide production following different stimuli of the respiratory burst in neutrophils and investigated the uptake andpotential metabolism (N-acetylation) of 5-aminosalicylic acid in lipopolysaccharide-primed and resting neutrophils. We found that 5-aminosalicylic acid and 4-aminosalicylic acid had defined scavenger properties in the dimethyl sulfoxide-NaOH or potassium superoxide systems, respectively, whereas compounds with a modified aminophenolic structure had no effects. At the cellular level, 5-aminosalicylic acid inhibited phorbol myristate acetate (100 ng/ml)-activated superoxide generation to 82.3 +/- 9.3%, the formylmethionyl leucyl peptide (10(-5) M) to 61.0+/- 6.8%, and the NaF; (20 mM)-stimutated production to 32.3 +/- 3.2%(X +/- SD, P < 0.01). The actions of the other drugs were less pronounced. Almost identical retention times (R(t) = 11.2 min) of H-3-labeled phorbol myristate acetate in the presence and absence of 5-aminosalicylic acid revealed no in vitro interactions. 5-Aminosalicylic acid permeates cells in a dose- and time-dependent manner; there was, however, no acetylation of 5-aminosalicylic acid regardless whether the cellshad been stimulated or not with lipopolysaccharide. From our results we suggest that (1) the extra- (scavenger) and intracellular inhibition of superoxide radicals by 5-aminosalicylic acid may be an important mechanism of action, (2) an intact aminophenolic structure may be necessary for such actions, and (3) the inability of inflammatory neutrophils to acetylate and, therefore, inactivate 5-aminosalicylic acid could be an important determinant for its local actions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 06:55:20