The NADPH oxidase inhibitor apocynin (acetovanillone) induces oxidative stress.
Apocynin (acetovanillone) is often used as a specific inhibitor of NADPH oxidase. In N11 glial cells, apocynin induced, in a dose-dependent way, a significant increase of both malonyldialdehyde level (index of lipid peroxidation) and lactate dehydrogenase release (index of a cytotoxic effect). Apocynin evoked also, in a significant way, an increase of H(2)O(2) concentration and a decrease of the intracellular glutathione/glutathione disulfide ratio, accompanied by augmented efflux of glutathione and glutathione disulfide. Apocynin induced the activation of both pentose phosphate pathway and tricarboxylic acid cycle, which was blocked when the cells were incubated with glutathione together with apocynin. The cell incubation with glutathione prevented also the apocynin-induced increase of malonyldialdehyde generation and lactate dehydrogenase leakage. Apocynin exerted an oxidant effect also in a cell-free system: indeed, in aqueous solution, it evoked a faster oxidation of the thiols glutathione and dithiothreitol, and elicited the generation of reactive oxygen species, mainly superoxide anions. Our results suggest that apocynin per se can induce an oxidative stress and exert a cytotoxic effect in N11 cells and other cell types, and that some effects of apocynin in in vitro and in vivo experimental models should be interpreted with caution.
Riganti
Chiara
C
Dipartimento di Genetica, Biologia e Biochimica, Università di Torino, Via Santena 5/bis, 10126 Torino, Italy.
Costamagna
Costanzo
C
Bosia
Amalia
A
Ghigo
Dario
D
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002952:Citric Acid Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D019803:Glutathione Disulfide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects*; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D000098:Acetophenones; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D013481:Superoxides; D008315:Malondialdehyde; C056165:acetovanillone; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D019255:NADPH Oxidases; D005978:Glutathione; D019803:Glutathione Disulfide