Characterization of the effect of photobiomodulation in vitro model of endothelial dysfunction and pharmacological strategies to potentiates this effect

• Grant number: 19/10037-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: September 30, 2020
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Gerson Jhonatan Rodrigues
• Grantee: Gabriel de Melo Arthur
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Endothelial dysfunction is described by the decreased capacity of endothelial cells to release nitric oxide (NO). NO is a powerful physiological modulator of vascular tone, regulating inflammatory processes (by activation of PPARg and inhibition of NF-ºB), for example. Because it is a free radical, NO reacts easily with molecules in which there is an unpaired electron, and therefore, is very unstable under physiological conditions. Superoxide anion (O2-) reduces NO bioavailability and activates NF-ºB, which has been found to be active in diseased cells of the cardiovascular system. Thus, increasing [NO] and decreasing [O2-] in the cardiovascular system may be a strategy for improving endothelial function and inflammatory profile. Such modulation can be achieved by the use of low-level LASER therapy (LLLT) or Photobiomodulation. Results from our laboratory indicate that red LASER (660 nm) can induce the release of NO from vascular tissue. There are indications in the literature that this range of LASER is able to reduce [O2-] and systemic inflammation. The increase of NO can be through the conversion of nitrate (NO2-) to NO, which makes the association with nitrite a possible means to potentiate the effect of LLLT. Another pharmacological strategy that can potentiate the effect of LASER is the blocking of multidrug resistance proteins (MRP). MRPs can pump cyclic guanosine monophosphate (cGMP) into the extracellular medium. The cGMP production is catalyzed by the soluble guanylate cyclase (GCs) enzyme, with the removal of two phosphate groups from the guanosine triphosphate (GTP) molecule. Since GCs are the main target of NO, inhibition of cGMP efflux by blocking MRPs would enhance the effect of LASER. Thus, the objective of this project is to test the hypothesis that red laser photobiomodulation (660 nm) is capable of improving endothelial function, as well as that its effects are potentiated by nitrite and/or MRP blockers. (AU)