Name: RAFAELA AIRES
Publication date: 20/08/2021
Advisor:
Name |
Role |
|---|---|
| SILVANA DOS SANTOS MEYRELLES | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| BRENO VALENTIM NOGUEIRA | External Examiner * |
| MARCELO PERIM BALDO | External Examiner * |
| SILVANA DOS SANTOS MEYRELLES | Advisor * |
| SONIA ALVES GOUVEA | Internal Examiner * |
Summary: The benefits of Kefir consumption are due, in part, to the rich composition of bioactive molecules released from fermentation. However, the bioactive components and mechanisms of action involved in the antihypertensive effect of this probiotic still need to be explored. A previous study sequenced 35 angiotensin-converting enzyme (ACE) inhibitory peptides in Kefir. Here, the in vivo actions of the Kef-1 peptide, an ACE inhibitor derived from Kefir, was evaluate in an angiotensin II-dependent hypertension model. Firstly, Kef-1 inhibitory activity on ACE was evaluate in vitro. In mice with 2-kidney, 1-clip (2K1C) hypertension, the short (3 days) and long-term (7 days) hemodynamic effects were evaluated after oral administration of Kef-1. For in vivo protocols, C57Bl/6 male mice were submitted to clipping of the left renal artery to produce 2K1C hypertension. The short (3 days) and long-term (7 days) hemodynamic effects were evaluated after oral administration of Kef-1. Furthermore, after 7 days of treatment, systemic and local (vascular smooth muscle cells, SMC) oxidative stress and inflammation were analyzed. Kef-1 was able to inhibit at 59.6% the in vitro activity ACE in comparation to captopril. After 3 hours, Kef-1 reduced (p<0.05) systolic BP (SBP), diastolic BP (DBP) and media BP (MBP) when compared with vehicle treatments (-25.8±3.9, -26.0±3.8, -26.4±4.3 mmHg, respectively). SBP, DBP and MBP also were reduced (p<0.05) after 7 days of Kef-1 treatment (-22.2±3.9; -31.6±2.6; MBP: -24.3±3.2 mmHg, respectively). Kef-1 reduced (p<0,05) HR in both short (~13%) and long-treatment (~7%). At 7 days following Kef-1, ROS production, lipidic peroxidation and DNA damage was lower in blood cells (p<0.05) when compared to the 2K1C group (~10%, ~23%, ~54%, respectively). In SMC, Kef-1 was able to reduce (p<0.05) ROS production (~22%) and cellular apoptosis (~58%) in comparation to the 2K1C group. Kef-1 contributed to attenuate NADPHox and mitochondrial participation in SMC. Furthermore, Kef-1 reduced SMC apoptosis (59%, p<0.05). The anti-inflammatory effect of Kef-1 was evidenced in the reduction (p<0.05) of the systemic levels of pro-inflammatory cytokines (TNFα: ~34%, IFNγ: ~22%, MCP1: ~33%, IL-6:~16%) and the activity of myeloperoxidase (~57%). In SMC, Kef-1 reduced by 75% (p<0.05) the intracellular levels of NO. The aorta of hypertensive 20 mice treated with Kef-1 showed lower thickness of wall (~28%, p<0.05) and partial restoration of endothelial structure. In conclusion, this study revealed the anti-hypertensive potential of the Kef-1 heptapeptide through its antioxidant and anti-inflammatory properties in an experimental model of Ang II-dependent hypertension. These new findings help to clarify the mechanisms involved in the benefits of Kefir beverage in the hypertension.
