title: Antioxidant activity and cytotoxicity as mediators of the neutrophil chemiluminescence inhibition by butylated hydroxytoluene.
abstract: The tissue damage found in some inflammatory and autoimmune diseases has been shown to be mediated by an increased activation of neutrophil effector functions. In this study, we investigated the inhibitory effect of the phenolic compound butylated hydroxytoluene (BHT) on reactive oxygen species (ROS) generation by opsonized zymosan-stimulated neutrophils, assessed by luminol- and lucigenin-enhanced chemiluminescence (CL-lum and CL-luc, respectively), and some aspects of its mechanism of action. BHT showed concentration-dependent: (a) inhibitory effect on CL-lum and CL-luc; (b) cytotoxic effect, expressed by increased lactate dehydrogenase leakage by the cells; (c) interaction with neutrophil membranes; (d) ROS scavenger activity. These biological effects were observed in the same range of concentrations (0-5 x 10(-5) mol/l). Taken together, the results suggest that inhibition of neutrophil chemiluminescence by BHT was a result of multiple mechanisms, especially a cytotoxic effect probably mediated by BHT interaction with neutrophils membranes, and the ROS scavenging effect.
authors.affiliation: Departamento de Física e Química, Faculdade de Cièncias Farmacêuticas de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Kabeya
authors.forename: A
authors.initials: A
authors.lastname: Kanashiro
authors.forename: A E C S
authors.initials: AE
authors.lastname: Azzolini
authors.forename: A C
authors.initials: AC
authors.lastname: Santos
authors.forename: Y M
authors.initials: YM
authors.lastname: Lucisano-Valim
mesh_terms: D000166:Acridines / Q000737:chemistry; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D049449:Luminescence; D008165:Luminol / Q000737:chemistry; D008560:Membrane Fluidity / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000166:Acridines; D000975:Antioxidants; D017382:Reactive Oxygen Species; D002084:Butylated Hydroxytoluene; C033472:10,10'-dimethyl-9,9'-biacridinium; D008165:Luminol; D007770:L-Lactate Dehydrogenase