Abstract:
Obesity and diabetes are the major risk factors for cardiovascular diseases being associated with increased reactive oxygen species (ROS) generation. We have previously demonstrated that monoamine oxidase (MAO), and mitochondrial enzyme with two isoforms, A and B, is a novel source of cardiac oxidative stress in rats with streptozotocin-induced diabetes. We hypothesized that MAO contributes to ROS generation in hearts isolated from rats with diet-induced obesity (24 weeks of high calorie junk food diet that lead to a prediabetic state). Cardiac MAO expression (immune fluorescence and qRT-PCR) and ROS level (spectrophotometry – ferrous oxidation xylenol orange assay, and immune fluorescence – dihydroethidium staining) were assessed in samples isolated from obese vs control rats. Experiments were performed in the presence vs absence of MAO A and B inhibitors (clorgyline and selegiline, 10 µM). Both MAO isoforms were increased in cardiac samples from diseased animals, being associated with high ROS generation. In vitro treatment with MAO inhibitors mitigated the ROS production in the hearts from obese rats. In conclusion, both MAO isoforms contribute to cardiac oxidative stress and can be targeted with the available armamentarium of MAO inhibitors in the settings of obesity and prediabetes.
Research supported by the university internal grant no. 6POSTDOC/1871/12.02.2020.
Key words: Monoamine oxidase; Oxidative stress; Obesity; Prediabetes; Rat heart.
