title: Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver.
abstract: The effect of apocynin on the activity of arylamine N-acetyltransferases (NATs) in excised liver samples was examined using eighteen Sprague-Dawley rats. Three groups of six animals each were fed a normal diet alone or a treatment of 50 or 100 mg/kg/day of apocynin via gavages for eight (8) weeks. Chronic in vivo administration of apocynin led to significant (p < 0.001) reduction of in vitro liver NAT activity up to 93% as compared with untreated rats (18.80 ± 2.10 μmols p-anisidine/min/μg liver protein). In vitro exposure of untreated liver homogenates to apocynin led to a dose-dependent inhibition of NAT activity with IC50 = 0.69 ± 0.02 mM. In silico modelling of apocynin tautomers and radical species into human NAT crystal structures supported the hypothesis that thiol functionalities in NAT enzymes may be crucial in apocynin binding. The involvement of human NAT enzymes in different pathological conditions, such as cancer, has encouraged the research for selective NAT inhibitors in both humans and animal models with possible chemopreventive properties.
authors.affiliation: Natural Products Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
authors.forename: Sheena
authors.initials: S
authors.lastname: Francis
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3JA, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Laurieri
authors.affiliation: Department of Basic Medical Sciences, Physiology section, University of the West Indies, Mona, Kingston 7, Jamaica.
authors.forename: Chukwuemeka
authors.initials: C
authors.lastname: Nwokocha
authors.affiliation: Natural Products Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
authors.forename: Rupika
authors.initials: R
authors.lastname: Delgoda
mesh_terms: D000098:Acetophenones / Q000737:chemistry* / Q000378:metabolism; D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D045424:Complex Mixtures / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D045424:Complex Mixtures; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C056165:acetovanillone; D001191:Arylamine N-Acetyltransferase