IMPACT OF QUERCETIN ON OXIDATIVE STRESS AND MITOCHONDRIAL HOMEOSTASIS DURING CARDIAC HYPERTROPHY
Mitochondria. Cardiac hypertrophy. Quercetin. Reactive oxygen species.
Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. Although ROS are essentials for several physiological processes, excessive amounts may damage cardiomyocyte components, compromising their function and thus triggering a number of adverse changes such as cardiac fibrosis, impaired contraction, cell death by necrosis and apoptosis. The mitochondrial electron transport chain (ETC) is a known source of ROS. Because mitochondria account for about 25% of the mass of cardiomyocytes, they are considered one of the most significant sources of ROS in the heart. Thus, mitochondria have been the target of several studies using cardiac hypertrophy models. The flavonoid quercetin, is a potent ROS scavenger and having several beneficial effects on the cardiovascular system, including antihypertrophic effects. In this work, we tested whether quercetin could attenuate the cardiac hypertrophy by improving the redox balance and mitochondrial homeostasis. To this hypothesis we treated mice with intraperitoneal injections of isoproterenol (30 mg/kg/day) for 4 consecutive days. On the fifth day, some of these animals were euthanized and the remaining mice were relocated to two subgroups. From that point on, one group received only isoproterenol (ISO group) (30 mg/kg/dia) and another group received isoproterenol and quercetin (ISO+QUE group) orally (10 mg/kg/day) for 4 more days. The animals treated with ISO for 4 days showed increased cardiac weight/tibia length ratio, increased total protein content, decreased sulfhydryl protein content, compromised antioxidant enzyme activity and high H2O2 production. Intervention with quercetin treatment from this point on was able to attenuate cardiac hypertrophy, reestablish sulfhydryl protein levels and antioxidant activity, in addition to effectively blocking the H2O2 production. In addition, we observed that isoproterenol hypertrophic stimulation decreases mitochondrial superoxide dismutase (MnSOD) expression and activity, while quercetin reverses this effect. Quercetin also protects mitochondria against opening of mitochondrial permeability transition pore (mPTP) in vivo and in vitro. Taken together, these results show that quercetin is able to attenuate isoproterenol-induced cardiac hypertrophy by improving mitochondrial function and redox balance.