A raising dawn of pentoxifylline in management of inflammatory disorders in Covid-19

Abstract

The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up-regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute lung injury and acute respiratory distress syndrome. Different repurposed had been in use in the management of Covid-19, one of these agents is pentoxifylline (PTX) which has anti-inflammatory and antioxidant properties. Therefore, the objective of the present mini-review is to highlight the potential role of PTX in Covid-19 regarding its anti-inflammatory and antioxidant effects. PTX is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate which stimulates protein kinase A and inhibits leukotriene and tumor necrosis factor. PTX has antiviral, anti-inflammatory and immunomodulatory effects, thus it may attenuate SARS-CoV-2-induced hyperinflammation and related complications. As well, PTX can reduce hyper-viscosity and coagulopathy in Covid-19 through increasing red blood cell deformability and inhibition of platelet aggregations. In conclusion, PTX is a non-selective phosphodiesterase drug, that has anti-inflammatory and antioxidant effects thereby can reduce SARS-CoV-2 infection-hyperinflammation and oxidative stress. Besides, PTX improves red blood cells (RBCs) deformability and reduces blood viscosity so can mitigate Covid-19-induced hyper-viscosity and RBCs hyper-aggregation which is linked with the development of coagulopathy. Taken together, PTX seems to be an effective agent against Covid-19 severity.