RESUMO
The benefits of kefir consumption are partially due to the rich composition of bioactive molecules released from its fermentation. Angiotensin-converting enzyme (ACE) inhibitors are bioactive molecules with potential use in the treatment or prevention of hypertension, heart failure, and myocardial infarction. Here, the in vivo actions of the Kef-1 peptide, an ACE inhibitor derived from kefir, were evaluated in an angiotensin II-dependent hypertension model. The Kef-1 peptide showed a potential anti-hypertensive effect. Additionally, Kef-1 exhibited systemic antioxidant and anti-inflammatory activities. In smooth muscle cells (SMCs), the Kef-1 peptide decreased ROS production through the reduced participation of NADPH oxidase and mitochondria. The aorta of 2K1C mice treated with Kef-1 showed lesser wall-thickening and partial restoration of the endothelial structure. In conclusion, these novel findings highlight the in vivo biological potential of this peptide demonstrating that Kef-1 may be a relevant nutraceutical treatment for cardiovascular diseases.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inflamação/metabolismo , Kefir , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Aorta/efeitos dos fármacos , Aorta/patologia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/citologiaRESUMO
Sildenafil (SIL) has potential as an interesting gastroprotective drug. However, the pathways of its protective effect still needs to be clarified, and its use as a potential gastroprotective agent validated. This study aims to evaluate the effects of SIL via modulation of oxidative stress in a NSAID-induced gastric lesion model. Male Swiss mice were divided into six groups: control (CON, water), nonsteroidal anti-inflammatory drug (NSAID, water), proton pump inhibitor (PPI, 30 mg/kg of lansoprazole), SIL 5 (5 mg/kg), SIL 25 (25 mg/kg) and SIL 50 (50 mg/kg). The animals were treated by gavage (a single dose) after 24 hours of fasting, and gastric lesions were performed after 30 minutes, with indomethacin (40 mg/kg, by gavage). After 6h, the animals were killed and the stomach was removed to evaluate reactive oxygen species (ROS) production, oxidation of macromolecules, quantification of antioxidant enzymes, DNA fragmentation, apoptosis and macroscopic and histologic analysis of gastric lesions. SIL exerts a dose-dependent gastroprotective effect against NSAID-induced mucosal injury, also reducing cytoplasmic levels of ROS and consequent oxidative damage to macromolecules. In addition, SIL increases nitric oxide bioavailability, antioxidant enzymes and gastric cellular viability, as well as restoring important factors involved in gastroprotection. Our results demonstrate that different doses of SIL prevent indomethacin-induced gastric ulcer in mice via different, but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms.