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The Beneficial Effect of Omega-3 PUFA and L-Arginine on Endothelial Nitric Oxide (NO) Bioavailability
Published in Robert Fried, Richard M. Carlton, Flaxseed, 2023
Robert Fried, Richard M. Carlton
The cells of the endothelium typically form NO from dietary L-arginine or nitrates with the help of synthase enzymes. There are three known (iso-)forms of the enzyme nitric oxide synthase (NOS): two are constitutive (cNOS) and the third is inducible (iNOS). The cNOS forms have two functions, one is brain constitutive, and the other is endothelial constitutive (eNOS). The third form is the inducible iNOS, which supplies the immune system cells with NO. Figure 3.2 illustrates NOS form and function.
Role of Vitamin D and Antioxidants in the Prevention and Treatment of Alzheimer’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Shilia Jacob Kurian, Ruby Benson, Sonal Sekhar Miraj, Mahadev Rao
The role of vitamin D as an anti-inflammatory and antioxidant has been widely studied. In AD patients, the reactive astrocytes and microglia surrounding the amyloid plaques induce inflammatory cytokines and chemokines around the aggregates. Vitamin D is a significant regulator of various cytokines, in particular, in stimulating cytokines and macrophages, which enhance the clearance of β-amyloid plaques in AD patients. Moreover, the active form of vitamin D directly exhibits its anti-inflammatory action on the transcriptomic level via its effect on the brain pericytes. Increased levels of reactive nitrogen and oxygen species produced by the damaged neurons, astrocytes, and microglia are seen in elderly patients or those with neurodegenerative diseases. These can induce the expression of inducible nitric oxide synthase (iNOS). The iNOS is an enzyme involved in the synthesis of nitric oxide (NO). Higher NO levels can cause cell death and further neuronal excitotoxicity. Several animal model studies have demonstrated that vitamin D suppresses the production and expression of iNOS, and thereby manage the oxidative stress. Moreover, vitamin D (i) upregulates the expression of several neurotrophins, (ii) increases the secretion of the anti-inflammatory cytokine (interleukin (IL)-4), (iii) reduces the secretion of pro-inflammatory cytokines (tumor necrosis factor-alpha; TNF-α) and interleukin-1 beta (IL-1β), and (iv) inhibits differentiation of dendritic cells (de Abreu et al. 2009; Landel et al. 2016; Dursun and Gezen-Ak 2019).
Subfamily Bombacoideae
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Wild Plants, 2020
Mariam I. Gamal El-Din, Fadia S. Youssef, Mohamed L. Ashour, Omayma A. Eldahshan, Abdel Nasser B. Singab
Nitric oxide (NO) is a signaling molecule playing a crucial role in the pathogenesis of inflammation. NO is generated biochemically through the oxidation of the terminal guanidine nitrogen atom from L-arginine by nitric oxide synthetase (NOS). Having three isoforms, endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS), nitric oxide synthase is an important cellular mediator of both physiological and pathological inflammatory processes. Endothelial NOS (eNOS) and neuronal NOS (nNOS) are constitutively expressed in the body under normal physiological conditions. However, inducible NOS (iNOS) is an inducible enzyme highly expressed by inflammatory stimuli. Overproduction of NO by inducible NOS occurs in response to different inflammatory mediators (e.g., tumor necrosis factor-α (TNF-α), interleukine-1β (IL-1β), and bacterial lipopolysaccharide (LPS)), aggravating the inflammatory process and acting synergistically with other inflammatory mediators. Many plants have recently proved to possess strong inhibitory potential of inducible NOS enzyme (iNOS), inhibiting overproduction of nitric oxide.
Therapeutic role of Azadirachta indica leaves ethanolic extract against diabetic nephropathy in rats neonatally induced by streptozotocin
Published in Ultrastructural Pathology, 2021
Abd El-Fattah B. M. El-Beltagy, Amira M.B. Saleh, Amany Attaallah , Reham A. Gahnem
Nitric oxide synthases (NOS) are groups of enzymes responsible for synthesis NO from L-arginine in the cells of mammals. Inducible nitric oxide synthase (iNOS) is one of these enzymes. Prabhakar67 found that hyperglycemia is implicated in lowering of iNOS levels in cultured murine mesangial cells. Furthermore, other reports have shown decreased iNOS immunoreactivity68 or unchanged iNOS69 in the renal cells of diabetic rats. In the present study, the immuno-reactivity of iNOS appeared low expressed in the renal tissues of STZ-induced diabetic rats if compared with control. The obtained result is in line with finding of Sönmez and Dündar.70 Lee et al.71 elucidated that, the decreased NO production in diabetic kidney is mainly attributed to the overproduction of ROS that closely associated with elevation of reactive nitrogen species (RNS). In contrast to our results, Kuloglu and Aydin72 found that, iNOS immunoreactivity is increased in the renal tissues of diabetic rats. The authors postulated that this is a compensatory mechanism against diabetes induced renal damage. Treatment with neem leaves extract revered the decreased iNOS immnoreactivity induced by diabetes. This result explains the potential antioxidant role of neem via scavenging of excessive free radicals produced by diabetes.
Role of the BMP6 protein in breast cancer and other types of cancer
Published in Growth Factors, 2021
Andrea Marlene García Muro, Azaria García Ruvalcaba, Lourdes del Carmen Rizo de la Torre, Josefina Yoaly Sánchez López
The presence of BMPRII, ALK2 and ALK3 receptors via BMP6 has been demonstrated in macrophages which, when activated, trigger a signal through two independent pathways, Smad (Smad1/4) and p38 (GATA4) producing the activation of IL-6 by binding to the BMP6 response element within its promoter. BMP6 also activates the expression of IL-1β in macrophages and this, in turn, the expression of inducible nitric oxide synthase (iNOS), in addition, TNF-α was activated and the fraction of cells in G1 increased (Lee et al. 2010, 2011; Hong et al. 2009). In addition to the pro-inflammatory effects observed in macrophages, BMP6 favored the function of natural killer (NK) cells, which are responsible for recognizing and destroying neoplastic cells, as well as contributing to the presentation of antigens for the priming of T monocytes, it was confirmed the expression of BMP6 (as well as BMP2, but not BMP4 or BMP7) in NK cells and ALK3 and BMPRII receptors (Robson et al. 2014).
Protective effect of aminoguanidine against lipopolysaccharide-induced hepatotoxicity and liver dysfunction in rat
Published in Drug and Chemical Toxicology, 2021
Farimah Beheshti, Mahmoud Hosseini, Mehdi Taheri Sarvtin, Ali Kamali, Akbar Anaeigoudari
It has also been reported that anti-inflammatory and anti-oxidant compounds can exert protective effects on organs (Mohebbati et al. 2017). In this regard, inducible nitric oxide synthase (iNOS) inhibitors has been shown to have significant cellular protective effects through reducing in lipid peroxidation and total nitrite level and applying anti-inflammatory, antioxidant and anti-apoptotic effects (Anaeigoudari et al. 2016a). Aminoguanidine (AG) is an iNOS inhibitor that has a wide range of physiological effects including suppression of inflammation, neuroprotective, inhibition of oxidative and nitrosative stress (Rodrigues et al. 2009). AG has also been reported to suppress DNA binding nuclear factor-κB (NF-κB) ultimately to inhibit the production of inflammatory cytokines (Díaz et al. 2014). Despite multiple reports about beneficial effects of AG on inflammatory responses and oxidative stress, however, its effect on liver dysfunction caused by LPS is still unclear. In this case, the current study was conducted to investigate the effect of AG on LPS-induced liver dysfunction in rat.