Background: During the initial phase of an infection, there is an upregulation of inducible nitric oxide synthase in the macrophages for the production of nitric oxide. This is followed by the recruitment of polymorphonuclear leukocytes (neutrophils) which release arginase. Arginase competes with inducible nitric oxide synthase for a common substrate L-arginine. Objective: To investigate whethe...

In the present study we carried out a screening of different Antiretroviral drugs (ARVs) for their potential pro-inflammatory effects on microglial cells. Efavirenz, neviparine, darunavir and atazanavir increased nitric oxide (NO) production in microglial cells activated with Gp120CN54 and interferon-γ. The stimulatory effect on NO production appeared to be mediated by inhibition of arginase (A...

Preliminary evidence in an animal model, that is, primary cultures of rat microglia cells, suggested that some antiretroviral drugs (ARVs), namely darunavir, atazanavir, efavirenz, and nevirapine, increase NO production through a mechanism involving the inhibition of arginase (ARG) activity. This study was conceived to investigate the effects of ARVs on ARG activity in a human experimental mode...

Polyamine synthesis from l-ornithine is essential for Leishmania growth. We have investigated the dependence of Leishmania infection on arginase, which generates l-ornithine, in macrophages from BALB/c, C57BL/6, and nitric oxide synthase II (NOS II)-deficient mouse strains. We have found that N(omega)-hydroxy-l-arginine (LOHA), a physiological inhibitor of arginase, controls cellular infection ...

OBJECTIVES We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. METHODS AND RESULTS After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visce...

The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimic...

Aim: Acetylsalicylic acid (ASA, aspirin), which is one of the most frequently used drugs in the world, causes severe gastric mucosal injury. Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS). NOS can be inhibited by Nω-nitro-L-arginine methyl ester (L-NAME) and stimulated by supplementing the diet with L-arginine (L-Arg). The aim of this study was to investigate th...

The superoxide radical anion (O # −d) produced during the catalytic activity of nitric oxide synthase (NOS) and cytochrome P-450 has been implicated in the oxidative denitrification of hydroxyguanidines ("C ̄NOH). The reactivity of the radiolytically generated O # −d radical with N-hydroxy--arginine (NHA) is pH dependent and appears to parallel the prototropic equilibrium of the hydroxyguanidin...

Arginases are enzymes that are involved in many human diseases and have been targeted for new treatments. Here a series of cinnamides was designed, synthesized and evaluated in vitro and in silico for their inhibitory activity against mammalian arginase. Using a microassay on purified liver bovine arginase (b-ARG I), (E)-N-(2-phenylethyl)-3,4-dihydroxycinnamide, also named caffeic acid phenylam...