1.
Circulating markers of nitric oxide homeostasis and cardiometabolic diseases: insights from population-based studies.
Bahadoran, Z, Mirmiran, P, Jeddi, S, Carlström, M, Azizi, F, Ghasemi, A
Free radical research. 2019;(4):359-376
Abstract
Emerging data suggest that impaired nitric oxide (NO) homeostasis has a key role in development of cardiometabolic disorders. The association between circulating levels of NO metabolites, i.e. nitrate and nitrite (NOx), and risk of chronic diseases has not yet been fully clarified. This work aims to address epidemiologic aspects of NO metabolism and discusses different physiologic and pathophysiologic conditions influencing circulating NOx. Further, cross-sectional associations of serum NOx with metabolic disorders are described and along the way, potential short-term and long-term power of serum NOx for predicting cardiometabolic outcomes are reviewed. Results from population-based studies show that circulating NOx is affected by aging, smoking habits, pregnancy, menopause status, thyroid hormones, and various pathologic conditions including type 2 diabetes, insulin resistance, hypertension, and renal dysfunction. Lifestyle factors, especially dietary habits, but also smoking habits and the degree of physical activity influence NO homeostasis and the circulating levels of NOx. Elevated serum NOx, due to increased iNOS activity, is associated with increased incidence of metabolic syndrome, different obesity phenotypes, and cardiovascular events.
2.
Oxidative stress and cardiovascular disease: new insights.
Pignatelli, P, Menichelli, D, Pastori, D, Violi, F
Kardiologia polska. 2018;(4):713-722
Abstract
The role of oxidative stress in the onset and progression of atherosclerosis and its impact on the development of cardiovascular events has been widely described. Thus, increased oxidative stress has been described in several atherosclerotic risk factors, such as hypertension, dyslipidaemia, peripheral artery disease, metabolic syndrome, diabetes, and obesity. Among others, specific oxidative pathways involving both pro-oxidant and antioxidant enzymes seem to play a major role in the production of reactive oxidant species (ROS), such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase, superoxide dismutase, and glutathione peroxidase. In this review, we will discuss: 1) the most relevant enzyme systems involved in the formation and detoxification of ROS, 2) the relationship between oxidative stress and cardiovascular risk, and 3) therapeutic implications to modulate oxidative stress.
3.
Inhibiting insulin resistance mechanisms by DTS phytocompound: an experimental study on metabolic syndrome-prone adipocytes.
Catanzaro, R, Lorenzetti, A, Allegri, F, Yadav, H, Solimene, U, Kumaraju, AK, Minelli, E, Tomella, C, Polimeni, A, Marotta, F
Acta bio-medica : Atenei Parmensis. 2012;(2):95-102
Abstract
The present study was designed to determine whether DTS a phytocompound endowed with antioxidant properties, could beneficially modulate nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) in adipocytes. Combined stimulation (CS-treatment) exerted by using 5 microg/ml of LPS together with 100 ng/ml of TNF-alpha significantly enhanced NO production in 3T3-L1 adipocytes. Preincubation of the adipocytes with DTS (10-30 mM) inhibited such phenomenon in a dose-dependent fashion. The production of NO was decreased by 52% at the concentration of 30mM of DTS. The decrease in NO production by DTS was associated also with a decrease in inducible nitric oxide synthase (iNOS) protein and iNOS mRNA expression. Nuclear factor-kappa B (NF-kappaB) was significantly enhanced by CS-treatment, while the pretreatment with 30 mM of DTS prevented the activity by 27%. IL-6 production in 3T3-L1 adipocytes was markedly increased by CS stimulus, and the enhanced secretion of IL-6 was suppressed in a dose-dependent manner by DTS. These results suggest that DTS regulates iNOS expression and NO production in adipocytes through the modulating activation of NF-kappaB and may have a potential clinical application within protocols designed for treating metabolic syndrome. (www.actabiomedica.it).
4.
The role of a disturbed arginine/NO metabolism in the onset of cancer cachexia: a working hypothesis.
Buijs, N, Luttikhold, J, Houdijk, AP, van Leeuwen, PA
Current medicinal chemistry. 2012;(31):5278-86
Abstract
Cancer cachexia is a complex catabolic state in patients with a malignancy, associated with increased morbidity and mortality. This syndrome is characterized by a redistribution of the body's protein content and a subsequent muscle wasting. The aetiology of this syndrome seems multifactorial, but remains unclear. It is suggested that this catabolic state occurs in response to the alterations in immune interactions between tumor and host. The amino acid arginine and its derivate nitric oxide (NO) play various roles in anti-tumor immune response and the body's homeostasis. Glutamine is the precursor for arginine de novo synthesis and the most abundant amino acid in the body, mainly stored in skeletal muscle. Tumors develop a protection mechanism against the specific anti-tumor attack of the immune system by recruiting myeloid derived suppressor cells (MDSC). The MDSC deplete arginine levels and disturb NO production. We here hypothesize that the perturbation of the arginine/NO metabolism plays a significant role in the aetiology of cancer cachexia. Arginine/ NO metabolism is disturbed in patients with cancer. The body will try to correct this perturbation by mobilizing arginine and glutamine from muscles. The decreased arginine levels and the disturbed NO production activate several cascades, which in turn inhibit protein synthesis and promote proteolysis, leading to cachexia. Cachexia remains one of the most frequent and damaging opportunistic syndromes in cancer patients. In this review we will elaborate on a new hypothesised concept and the underlying mechanisms of this syndrome. New studies are essential to ground this hypothesis and to develop interventions to break through the pathological mechanisms underlying cachexia.