53 research outputs found
Alleviation of mao-related oxidative stress by antidiabetic drugs : of mice and men : [abstract]
Monoamine oxidase contribution to valvular heart disease : more than meets the eye : [abstract]
Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues
A substantial body of evidence indicates that pharmacological activation of mitochondrial ATP-sensitive potassium
channels (mKATP) in the heart is protective in conditions associated with ischemia/reperfusion injury. Several mechanisms have
been postulated to be responsible for cardioprotection, including the modulation of mitochondrial respiratory function. The
aim of the present study was to characterize the dose-dependent effects of novel synthetic benzopyran analogues, derived from
a BMS-191095, a selective mKATP opener, on mitochondrial respiration and reactive oxygen species (ROS) production in isolated
rat heart mitochondria. Mitochondrial respiratory function was assessed by high-resolution respirometry, and H2O2 production
was measured by the Amplex Red fluorescence assay. Four compounds, namely KL-1487, KL-1492, KL-1495, and KL-1507, applied
in increasing concentrations (50, 75, 100, and 150 �mol/L, respectively) were investigated. When added in the last two
concentrations, all compounds significantly increased State 2 and 4 respiratory rates, an effect that was not abolished by
5-hydroxydecanoate (5-HD, 100 �mol/L), the classic mKATP inhibitor. The highest concentration also elicited an important
decrease of the oxidative phosphorylation in a K+ independent manner. Both concentrations of 100 and 150 �mol/L for
KL-1487, KL-1492, and KL-1495, and the concentration of 150 �mol/L for KL-1507, respectively, mitigated the mitochondrial
H2O2 release. In isolated rat heart mitochondria, the novel benzopyran analogues act as protonophoric uncouplers of
oxidative phosphorylation and decrease the generation of reactive oxygen species in a dose-dependent manner
Reversible Inhibition Monoamine Oxidase - A Improves Vascular Dysfunction in Canine Carotid Arteries Exposed to Angiotensin II
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