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Inhibition of intestinal peroxidase activity by nonsteroidal antiinflammatory drugs

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Title Inhibition of intestinal peroxidase activity by nonsteroidal
antiinflammatory drugs
 
Creator Chatterjee, Ratna
Bandyopadhyay, Uday
Bhattacharya, Dipak
Banerjee, Ranajit K
 
Subject Cell Biology & Physiology
 
Description The peroxidase activity of the mitochondrial fraction of rat intestine is inhibited in vitro by non-steroidal antiinflammatory drugs (NSAIDs), such as indomethacin (IMN) and acetylsalicylic acid (ASA), the former being more potent than the latter. The peroxidase was solubilised by cetab-NHaC1 extraction and purified to apparent homogeneity by Sephadex G-150 gel filtration and affinity chromatography on Con-A Sepharose. The purified enzyme activity was 80% inhibited by 150/z M IMN and 50% by
2.67 mM ASA. IMN could also inhibit lactoperoxidase activity to the same extent but not the horseradish peroxidase activity.The inhibition of peroxidase-catalysed iodide oxidation by IMN and ASA was optimal at pH 5.5 and 4.5, respectively. Kinetic studies revealed that the inhibition by IMN was competitive with respect to iodide or guaiacol, while the inhibition by ASA was noncompetitive and reversible in nature. Studies of some structural analogues showed that indole-3-acetic acid was as effective as IMN, while salicylic acid was more potent than ASA. Spectral studies showed a small bathochromic shift of the Soret band of the enzyme by IMN, suggesting its possible interaction at or near the heme moiety. The competitive nature of IMN may be explained as due to its oxidation by the peroxidase to a product absorbing at 412 nm, the formation of which is inhibited by iodide. We suggest that IMN inhibits intestinal peroxidase activity by acting as a competitive substrate for the enzyme. As intestinal peroxidase is mainly contributed by the invading eosinophils, NSAIDs may affect the host defence mechanism by inhibiting the activity of the enzyme.
 
Publisher Elsevier
 
Date 1993
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2309/1/BIOCHIMICA_ET_BIOPHYSICA_ACTA__V._1161__(_2%2D3_)_168%2D176;1993[51].pdf
Chatterjee, Ratna and Bandyopadhyay, Uday and Bhattacharya, Dipak and Banerjee, Ranajit K (1993) Inhibition of intestinal peroxidase activity by nonsteroidal antiinflammatory drugs. BBA - Biochimica et Biophysica Acta, 1161 (2-3). pp. 168-176.
 
Relation http://www.eprints.iicb.res.in/2309/