Assessment of nitric oxide metabolites concentrations in plasma, saliva, and breast milk and their relationship in lactating women.

Nitric oxide (NO) plays a role in many biological mechanisms. The amounts of physiologically produced NO are associated with the concentrations of its metabolites nitrate and nitrite. This study investigated whether there is any association between the concentrations of NO metabolites nitrate, nitrite, and nitrosylated species (RXNO) in mature breast milk, saliva, and plasma in healthy lactating women (N = 30). We hypothesized that the NO metabolites concentrations in plasma are associated with those found in saliva and in breast milk. NO metabolites concentrations were measured using chemiluminensce-based assays. Nitrate concentrations in breast milk are twice as much as plasma concentrations, whereas nitrate concentrations in saliva are about eightfold higher (both P < 0.001). Similar differences were found when nitrite concentrations were taken into consideration. RXNO concentrations in breast milk were negligible, and RXNO concentrations in saliva were approximately sixfold higher than those found in plasma samples (P < 0.0001). Nitrate concentrations in plasma are associated with nitrate concentrations in saliva (rs = 0.474, P = 0.004). However, no significant association was found between nitrate concentrations in breast milk and in plasma (P > 0.05). Our results show a significant association between nitrate concentrations in plasma with those found in saliva, whereas all other relationships were not significant. In conclusion, this report shows for the first time that the physiological concentrations of NO metabolites in human breast milk are probably independent of circulating NO metabolites concentrations and may depend mostly on endogenous NO synthesis in the breast. These findings may have clinical implications for newborns and lactating women.

Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress.

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.