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The Role of Oxidative Stress in Anti-tumor Necrosis Factor Antibody Treatment in Crohn's Disease

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Administration of anti-tumor necrosis factor alpha antibodies [anti-TNF]-alpha represents a therapeutic approach aimed to diminish the effects of tumor necrosis factor [TNF]- alpha in Crohn's disease [CD]. Blockade of its action should be related to various changes including those in immune and inflammatory response. There is a growing body of experimental data to suggest that the chronically inflamed intestine may be subjected to considerable oxidative stress. The aim of this study was to study the impact of therapy with anti-TNF [infliximab] on Crohn's disease activity index [CDAI], markers of inflammatory activity and oxidative stress. Fourteen patients with active CD received 5mg/kg of infliximab in a single intravenous infusion. CDAI, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fibrinogen [FBG], alpha-1 antitrypsin [AAT], albumin [ALB], ceruloplasmin apoprotein [CP], ferroxidase activity of CP [FOACP], specific enzymatic activity of CP [SEACP] and conjugated dienes [DIE] were determined before treatment in month 0 [M 0], in 1st control period in month 1 [M 1] and in 2nd control period in month 5 [M 5] after treatment. In clinical activity a sustained significant decrease in CDAI was observed, with a significant drop in M 1, remaining in M 5. A significant decrease in ESR in M 1, accompanied by insignificantly reduced levels of CRP and FBG was present. During the further follow up in M 5 a slight increase of ESR, CRP and FBG was noticed. A significant decrease of AAT in M 1 was present; this decrease was followed by a significant increase in M 5. Ceruloplasmin apoprotein levels dropped in M 1, with further slight insignificant increase in M 5. A significant increase of ALB sustaining in M 5 was present. The levels of DIE slightly decreased in M 1 and significantly in M 5, together with the slight increase of the FOACP and SEACP in M 1 and significant increase in M 5. We conclude, that oxidative stress may be important in the pathogenesis and perpetuation of tissue injury in CD patients. The decreasing levels of DIE together with the increase of the FOCP and SEACP after infliximab treatment together with changes of markers of inflammatory activity, can participate in the improvement of clinical status of patients with CD.
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Keywords: Albumin; Crohn's disease; alpha-1 antitrypsin; ceruloplasmin apoprotein; conjugated dienes; ferroxidase activity; infliximab; oxidative stress; pathogenesis; tumor necrosis factor-alpha

Document Type: Research Article

Publication date: 2012-10-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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