Bruna Gazzi de Lima Seolin

Sulforaphane improves oxidative status without attenuating the inflammatory response or cardiac impairment induced by ischemia–reperfusion in rats

Sulforaphane, a natural isothiocyanate, demonstrates cardioprotection associated with its capacity to stimulate endogenous antioxidants and to inhibit inflammation. The aim of this study was to investigate whether sulforaphane is capable of attenuating oxidative stress and inflammatory responses through the TLR4/MyD88/NFκB pathway, and thereby could modulate post-ischemic ventricular function in isolated rat hearts submitted to ischemia and reperfusion. Male Wistar rats received sulforaphane (10 mg·kg(-1)·day(-1)) or vehicle i.p. for 3 days. Global ischemia was performed using isolated hearts, 24 h after the last injection, by interruption of the perfusion flow. The protocol included a 20 min pre-ischemic period followed by 20 min of ischemia and a 20 min reperfusion. Although no changes in mechanical function were observed, sulforaphane induced a significant increase in superoxide dismutase and heme oxygenase-1 expression (both 66%) and significantly reduced reactive oxygen species levels (7%). No differences were observed for catalase and glutathione peroxidase expression or their activities, nor for thioredoxin reductase, glutaredoxin reductase and glutathione-S-transferase. No differences were found in lipid peroxidation or TLR4, MyD88, and NF-κB expression. In conclusion, although sulforaphane was able to stimulate endogenous antioxidants modestly, this result did not impact inflammatory signaling or cardiac function of hearts submitted to ischemia and reperfusion.

Role of Redox Homeostasis and Inflammation in the Pathogenesis of Pulmonary Arterial Hypertension

This review addresses pulmonary arterial hypertension (PAH), an incurable disease, which determines high morbidity and mortality. Definition of the disease, its characteristics, classification, and epidemiology are discussed. A difficulty in the diagnosis of PAH due to the lack of symptoms specificity is highlighted. Echocardiographic analysis and electrocardiogram of patients help in the diagnosis and in the follow up of the disease. Nevertheless, right ventricle (RV) catheterization constitutes the gold standard for diagnosing PAH. Oxidative stress and inflammation, in an interactive manner, play a major role in the development of pulmonary vascular remodeling and consequent increase of pulmonary pressure. The latter results in an increase in RV afterload, culminating with RV hypertrophy, which may progress to failure. Both clinical and experimental studies have shown increased oxidative stress and inflammation, not only in lungs and pulmonary vasculature but also in RV. The use of experimental models, such as the monocrotaline-induced PAH, has helped in the understanding of the pathophysiology of PAH, as well as in the development of new therapeutic strategies. In addition to the traditional therapeutics, the use of therapeutic interventions capable of modulating oxidative stress and inflammation may offer newer strategies in the prevention as well as management of this disease.

Oxidative Stress Influence in the Development of Pulmonary Arterial Hypertension

This review addresses pulmonary arterial hypertension (PAH), an incurable disease that determines high morbidity and mortality. Diagnosis is usually performed at advanced stages of the disease, because symptoms are unspecific. Treatment is expensive and do not promote reversion of the disease, only demonstrates some improvement in patients quality of life. Oxidative stress is one of the mechanisms involved in the pathogenesis of PAH, contributing to the development of pulmonary vascular remodeling and consequent increase of pulmonary pressure. This results in an enhanced right ventricle (RV) afterload, determining RV hypertrophy which progresses to RV failure. Literature has shown increased oxidative stress not only in pulmonary vessels, but also in lungs and RV of pulmonary hypertensive patients and experimental animals. The use of experimental models has contributed to the understanding of the pathophysiology of PAH, and to the development of new therapeutic strategies. Therapeutics focused on the modulation of oxidative stress has been considered very promising. Some of these therapeutic interventions constitute of substances that modulate gene expression promoting antioxidant adaptations.