D-Amphetamine-Induced Hydrogen Peroxide Production in Skeletal Muscle is Modulated by Monoamine Oxidase Inhibition

Abstract

The aim of this paper was to study the influence of d-amphetamine administration as a sympathomimetic drug on the synthesis of hydrogen peroxide (H2O2) in mouse soleus muscle and to investigate the modulating effects of pargyline, an inhibitor of monoamine oxidase (MAO) in this context. Charles River mice were assigned to four groups: Control, d-amphetamine treated, pargyline treated, and amphetamine + pargyline treated. Their soleus muscles were removed 0, 15, 30, 60, and 120 min after treatment. The amount of hydrogen peroxide formation within the muscles was estimated using an indirect method. The control data showed a continuous production of hydrogen peroxidase. Pargyline administration lead to an initial increase of H2O2 production that later faded below control levels. Administration of amphetamine finally stimulated H2O2 production much above control levels. When combining amphetamine and pargyline treatment, H2O2 production was accelerated in the initial phase but dropped to control levels at 30 min. It is concluded that in skeletal muscle MAO is an important source of hydrogen peroxide production triggered by amphetamine administration and that this tissue plays a hitherto not described role in oxidizing circulating biogenic monoamines.

Contribution of Catecholamine Reactive Intermediates and Oxidative Stress to the Pathologic Features of Heart Diseases

“…The highly reactive HO [183] causes oxidative stress-related damage, especially in organs with very low antioxidant defenses such as the heart [395,396]. In fact, MAO inhibitors have been found to decrease the incidence and severity of myocardial lesions following catecholamine administration [397,398].…”

Adrenaline and Noradrenaline: Partners and Actors in the Same Play"

“…Dopamine, tyramine, and tryptamine are oxidized with equal affinity by MAO-A and MAO-B (Glover et al, 1977). Pargyline inhibits both MAO-A and MAO-B (Blaha et al, 1996, Carvalho et al, 2001, Carmo et al, 2003, Duarte et al, 2004. MAO-A appears to be the main enzyme in the metabolism of 5-HT and NA, while the location of MAO-B, abundant in serotonergic neurons, remains under debate (Abell and Kwan, 2001).…”

“…Of relevance, the oxidative deamination of catecholamines by MAO leads to another relevant product, hydrogen peroxide (H 2 O 2 ) which subsequently may be converted into the highly reactive hydroxyl radical (HO • ) (Valko et al, 2007), that may cause oxidative stressrelated damage (Carvalho et al, 2001, Duarte et al, 2004, Vaarmann et al, 2010, Costa et al, 2011.…”

Stress oxidativo e dano oxidativo muscular esquelético: influência do exercício agudo inabitual e do treino físico

“…Tendo em consideração os tempos de maior ou menor actividade das fontes de ERO atrás referidas, a figura 9 ilustra, de forma grosseira, a hipotética contribuição relativa de cada uma dessas fontes, durante e após o exercício físico agudo (4,33,34) . Um outro possível mecanismo de formação de ERO durante a contracção muscular esquelética pode estar relacionado com a oxidação das catecolaminas circulantes (23,35) . Estas hormonas são normalmente inactivadas in vivo de duas formas: i) ou por via enzimática, pela acção da Monoamina Oxidase (MAO) e da Catecol-O-Metiltransferase (COMT), ou então ii) por via não enzimática, pela sua própria auto-oxidação, que ocorre normalmente quando as vias enzimáticas estão saturadas (121) .…”