title: Activities of apocynin in cytotoxicity assays of potential pathological relevance.
abstract: Low levels of some reactive oxygen and nitrogen species (ROS, RNS) are of physiological importance; but high levels result in oxidative stress and can perturb many cell functions including signal transduction and transport, and contribute to aging and chronic diseases. Apocynin (1-(4-hydroxy-3-methoxyphenyl)ethanone) is a phytochemical with reported antioxidant activities in some experimental models of human disease. The major objectives of the current study were to test the antioxidant capacity of apocynin in a hemin-peroxide assay, and test its capacity to moderate pro-oxidant-dependent inhibition of a cell function-endocytic transport. Apocynin, tested at concentrations up to 20μM, did not exhibit statistically significant antioxidant activity (94.3±7.8% relative to controls, p>0.05) in the oxidation assay. When tested against the inhibition of endocytic transport by hydrogen peroxide, apocynin treatment did not significantly rescue such inhibition in the cell types tested (p>0.05, relative to peroxide alone). When cells were treated with a cytotoxic protein aggregate that increased both ROS and RNS, apocynin treatment only inhibited production of the latter (30.0±3.6% inhibition relative to controls without apocynin, p<0.05). The results provide evidence that apocynin, unlike other phytochemicals such as curcumin, does not exhibit antioxidant activity in the heme-peroxide assay. The results also provide the first evidence that apocynin does not rescue hydrogen peroxide-mediated inhibition of endocytic transport, nor prevent hydrogen peroxide production by a cytotoxic protein aggregate. In the latter toxicity assay, however, apocynin could moderate oxidative stress by decreasing cellular levels of RNS.
authors.affiliation: Nutrition and Metabolism Research Laboratory, Biomedical Physiology BPK, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Wong
authors.affiliation: Nutrition and Metabolism Research Laboratory, Biomedical Physiology BPK, Simon Fraser University, Burnaby, BC, Canada; Department of Neurology, Far Eastern Memorial Hospital, Taiwan.
authors.forename: Vai Hong
authors.initials: VH
authors.lastname: Fong
authors.affiliation: Nutrition and Metabolism Research Laboratory, Biomedical Physiology BPK, Simon Fraser University, Burnaby, BC, Canada. Electronic address: avvieira@sfu.ca.
authors.forename: Amandio
authors.initials: A
authors.lastname: Vieira
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C056165:acetovanillone; D006861:Hydrogen Peroxide
keywords: Antioxidant; Apocynin; Cytotoxicity; Endocytic transport; Hydrogen peroxide; Reactive nitrogen species