Trimetazidine and COVID-19-induced acute cardiac injury: a missed key

International Journal of Clinical Pharmacy -     

Hemolytic anemia in COVID-19

Annals of Hematology - COVID-19 is a global pandemic triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 entry point involves the interaction with...     

The Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19

Inflammation - SARS-CoV-2 by the direct cytopathic effect or indirectly through the propagation of pro-inflammatory cytokines could cause endothelial dysfunction (ED) and oxidative stress (OS). It...     

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

Inflammopharmacology - 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...     

Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective

Inflammopharmacology - SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) has been identified as the source of a world coronavirus pandemic in 2019. Covid-19 is considered a main...     

High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons

Inflammopharmacology - High-mobility group box 1 (HMGB1), a multifunctional nuclear protein, exists mainly within the nucleus of all mammal eukaryotic cells. It is actively secreted by the necrotic...     

Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena

Neprilysin (NEP) is a transmembrane zinc-dependent metalloproteinase that inactivates various peptide hormones including glucagon-like peptide 1 (GLP-1). NEP inhibitors may be effective in the management of type 2 diabetes mellitus (T2DM) by increasing the circulating level of GLP-1. However, acute-effect NEP inhibitors may lead to detrimental effects by increasing blood glucose independent of GLP-1. These findings suggest a controversial point regarding the potential role of NEP inhibitors on glucose homeostasis in T2DM patients. Therefore, this perspective aimed to clarify the controversial points concerning the role of NEP inhibitors on glucose homeostasis in T2DM. NEP inhibitors may lead to beneficial effects by inhibition of NEP, which is involved in the impairment of glucose homeostasis through modulation of insulin resistance. NEP increases dipeptidyl peptidase-4 (DPP4) activity and contributes to increasing active GLP-1 proteolysis so NEP inhibitors may improve glycemic control through increasing endogenous GLP-1 activity and reduction of DPP4 activity. Thus, NEP inhibitors could be effective alone or in combination with antidiabetic agents in treating T2DM patients. However, long-term and short-term effects of NEP inhibitors may lead to a detrimental effect on insulin sensitivity and glucose homeostasis through different mechanisms including augmentation of substrates and pancreatic amyloid deposition. These findings are confirmed in animal but not in humans. In conclusion, NEP inhibitors produce beneficial rather than detrimental effects on glucose homeostasis and insulin sensitivity in humans though most of the detrimental effects of NEP inhibitors are confirmed in animal studies.