RESUMO
The renin-angiotensin-aldosterone system is a neurohormonal system responsible for maintaining homeostasis of fluid regulation, sodium balance, and blood pressure. The complexity of this pathway enables it to be a common target for blood pressure and volume-regulating medications. The mineralocorticoid receptor is one of these targets, and is found not only in the kidney, but also tissues making up the heart, blood vessels, and adipose. Mineralocorticoid receptor antagonists have been shown to slow progression of chronic kidney disease, treat refractory hypertension and primary aldosteronism, and improve morbidity and mortality in management of heart failure with reduced ejection fraction. The more well-studied medications were derived from steroid-based compounds, and thus come with a distinct side-effect profile. To avoid these adverse effects, developing a mineralocorticoid receptor antagonist (MRA) from a non-steroidal base compound has gained much interest. This review will focus on the novel non-steroidal MRA, Finerenone, to describe its unique mechanism of action while summarizing the available clinical trials supporting its use in patients with various etiologies of cardiorenal disease.
Assuntos
Antagonistas de Receptores de Mineralocorticoides , Receptores de Mineralocorticoides , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Receptores de Mineralocorticoides/metabolismo , Naftiridinas/efeitos adversos , Sistema Renina-AngiotensinaRESUMO
Canthin-6-one (1), isolated from Zanthoxylum chiloperone (Rutaceae), possesses a broad sprectum of antifungal and leishmanicidal activities. In this study, we have examined the antiparasitic effects of canthin-6-one (1), 5-methoxycanthin-6-one (2), canthin-6-one N-oxide (3), as well as that of the total alkaloids of Zanthoxylum chiloperone stem bark, in Balb/c mice infected either acutely or chronically with Trypanosoma cruzi. The compounds were administered orally or subcutaneously at 5mg/kg/day for 2 weeks, whereas the alkaloidal extract was given at 50mg/kg/day for 2 weeks. The antiparasitic activity was compared with that of benznidazole given at 50mg/kg/day for 2 weeks. In the case of acute infection, parasiteamia was significantly reduced following oral treatment with canthin-6-one (1). Moreover, the total alkaloids of Zanthoxylum chiloperone stem bark led to high levels of parasitological clearance. Seventy days post-infection, the serological response in the acute model was significantly different between oral canthin-6-one (1) and benznidazole-treated mice. Chronic model of the disease showed that both canthin-6-one (1) and the alkaloidal extract at the above dosage induced 80-100% animal survival compared to untreated controls. These results indicate that canthin-6-one (1) exhibits trypanocidal activity in vivo in the mouse model of acute or chronic infection. This is the first demonstration of anti-Trypanosoma cruzi activity for a member of this chemical group (canthinones). Considering the very low toxicity of canthin-6-one (1), our results suggest that long-term oral treatment with this natural product could prove advantageous compared to the current chemotherapy of Chagas disease.