Abstract
Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19.
Highlights
Disseminated intravascular coagulation (DIC) is a clinical syndrome with high mortality caused by activation of systemic intravascular coagulation [1]
To investigate the effects of ultramicronized palmitoylethanolamide (um-PEA) on blood coagulation function and fibrinolytic system of rats, we detected the changes in plasma markers for DIC after oral administrations of um-PEA 30 min before and 1 h after the start of infusion of LPS
To confirm the reduction in mast cells (MCs) degranulation, we evaluated the expression of chymase and tryptase, two mast-cell-derived serine peptidases, in lungs
Summary
Disseminated intravascular coagulation (DIC) is a clinical syndrome with high mortality caused by activation of systemic intravascular coagulation [1]. It usually develops as a critical complication in patients with life-threatening conditions, such as severe infection, severe sepsis, malignancies, severe trauma, placental abruption, and obstetric calamities [2]. 2020, the WHO declared COVID-19 as a pandemic worldwide that represents a serious public health risk [4]. The high susceptibility of the population is responsible for the raised incidence of the distribution worldwide so that COVID-19 has become a serious public health problem. Intravenous infusion of lipopolysaccharide (LPS) has gained wide acceptance as an experimental model of DIC [10]
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