Influence of sulphasalazine and mesalazine on cellular and biochemical oxygen metabolite production. Effect of in vivo administration and an in vitro analysis.
Oxidative damage has been implicated in the pathogenesis of inflammatory bowel disease. In the present study sulphasalazine and mesalazine (5-aminosalicylic acid) in vitro were shown to possess scavenging activity and to attenuate the production of oxygen metabolites by neutrophils. In a double-blind randomized crossover study, with five patients with inflammatory bowel disease in remission and four healthy controls, we evaluated the influence of in vivo administration of sulphasalazine and mesalazine on the neutrophil oxygen metabolite production in vitro. Apart from a small but significant increase in the neutrophil H2O2 and O2 production by sulphasalazine, in particular in controls, in vivo administration of both drugs hardly affected the oxygen metabolite-producing capacity of the cells. This observation was confirmed by in vitro preincubation of neutrophils with the drugs and subsequent oxygen metabolite production analysis. It is concluded that sulphasalazine and mesalazine do not influence the oxidative capacity of neutrophils, but scavenge and attenuate the production of oxygen metabolites when present in the immediate surroundings of the cells. Thus, protection against oxidative damage is definitely one of the modes of action of these drugs.
Dept. of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.
H W
HW
Verspaget
M N
MN
Aparicio-Pagés
S
S
Verver
P M
PM
Edelbroek
J C
JC
Hafkenscheid
G E
GE
Crama-Bohbouth
A S
AS
Peña
I T
IT
Weterman
C B
CB
Lamers
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D019804:Mesalamine; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D012460:Sulfasalazine; D019804:Mesalamine; D010100:Oxygen