China
Africa
Explore chapters and articles related to this topic
Nitric Oxide as a Signaling Molecule in the Systemic Inflammatory Response to LPS
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Reactions between NO and glutathione not only deplete GSH but generate additional reactive species (e.g., GS · and GS03H) and lower the cellular levels of the antioxidants ascorbic acid and α-tocopherol, which are normally maintained by GSH (Table 2). In contrast, interactions between NO and GSH may also have a positive effect in that they reduce NO reactions with and metal-sulfur clusters that would otherwise lead to the formation of toxic intermediates. However, this scavenging effect of GSH would occur only as long as favorable GSH:NO ratios were maintained within the cell. Finally, nitroso-glutathione is relatively stable and may provide a long-term source of reactive nitrosothiols (7). Indeed, nitrosoglutathione has been shown to mimic the vasodilatory effects of the NO donors nitroglycerine and nitroprusside (9,69).
Glutathione and Glutathione Derivatives: Possible Modulators of Ionotropic Glutamate Receptors
Published in Christopher A. Shaw, Glutathione in the Nervous System, 2018
Réka Janáky, Vince Varga, Zsolt Jenei, Pirjo Saransaari, Simo S. Oja
Both extra- and intracellular GSH may form nitrosoglutathione (Hogg, Singh, and Kalyanaraman 1996; see also Cuénod and Do, chapter 12, this volume) and hence serve as a buffer of intra- and extracellular NO. S-Nitrosoglutathione may react with GSH and generate nitrous oxide and GSSG (Hogg et al. 1996). The reduction of the latter is inhibited by S-nitrosoglutathione (Becker, Gui, and Schirmer 1995). Both release of nitrous oxide and accumulation of GSSG may result in a short- and long-term downregulation of the NMDA receptor function (Manzoni et al. 1992; Janáky et al. 1993a; Lipton et al. 1993). However, more experimental work is needed to prove this hypothesis.
Regulation of cytochrome P450 enzyme activity and expression by nitric oxide in the context of inflammatory disease
Published in Drug Metabolism Reviews, 2020
Edward T. Morgan, Cene Skubic, Choon-myung Lee, Kaja Blagotinšek Cokan, Damjana Rozman
Several therapeutic drugs release NO (e.g. sodium nitroprusside (SNP) or S-nitrosoglutathione (GSNO)), or release NO upon metabolism (e.g. glyceryl trinitrate (GTN)). SNP is a vasodilator used for treatment of acute heart failure and hypertensive crises, whereas GTN is given sublingually for the treatment of angina. GSNO has undergone more than 20 clinical trials, mostly in cardiovascular diseases (Broniowska et al. 2013). Studies in isolated perfused rat livers demonstrated the loss of P450 heme and P450 activities within 30–60 min of perfusion with SNP or the NO donor isosorbide dinitrate (ISDN) (Vuppugalla and Mehvar 2004a, 2004b). Effects of NO on drug metabolizing P450s were seen in less than one hour and varied depending on the isoform involved. CYP2B1/2 activity was one of the most sensitive. Most P450 protein levels were unchanged following these short treatments. The NO donors inhibited P450 activities at 2–4 fold lower concentrations than they decreased total P450, and to a much greater extent (80–85%), suggesting that heme dissociation was not the primary mechanism. Kinetic analyses showed that ISDN or SNP reduced the Vmax of 2C11, 2B1/2, 3A2, 2E1 and 1A1/2 in the perfused livers. Kms for 2B1/2 and 2D1 were unchanged, the Km of 2C11 increased, and the Km of 1A1/2 decreased (Vuppugalla and Mehvar 2005). The Km effects were hypothesized to be due to thiol modification of the enzymes, because treatment of the microsomes with dithiothreitol tended to reverse the declines in activities after 1 hr of SNP treatment, less so after 30 min.
Role of Nitric Oxide in the Development of Cataract Formation in CdCl2-induced Hypertensive Animals
Published in Current Eye Research, 2018
Apurva Yadav, Rajesh Choudhary, Surendra H. Bodakhe
The lenticular oxidative stress is the key mechanism for inducing cataract. The lenticular oxidative stress signifies by the depletion of antioxidants (SOD, CAT, GPx, and GSH) and elevation of MDA and ROS (reactive oxygen species) level, resulting in molecular damage of lenticular cells followed by cataract formation.44 The present study (Table 1) revealed that CdCl2 treatments decreased the lens antioxidants (GSH, CAT, SOD, and GPx) and increased the lens MDA and nitrite level (Figure 3). This pathological condition is exacerbated by local application of S-nitrosoglutathione and alleviated by local application of L-NAME. Additionally, antihypertensive drug (amlodipine) treatments reduced the risk of lenticular oxidative stress concomitant with the reduction of lens nitrite level. This result gives the evidence that modulation of NO content in lens interferes with the lenticular antioxidant defense system in a hypertensive subject.
Encapsulation of S-nitrosoglutathione: a transcriptomic validation
Published in Drug Development and Industrial Pharmacy, 2019
Ramia Safar, Rémi Houlgatte, Alain Le Faou, Carole Ronzani, Wen Wu, Luc Ferrari, Hélène Dubois-Pot-Schneider, Bertrand H. Rihn, Olivier Joubert
The therapeutic use of nitric oxide (NO•) is limited by a short half-life in the body, namely less than 5 min [1,2]. This is identical for either free form [3] or nitrosated molecules, e.g. of nitroglycerin. For the latter, the rapid emergence of tolerance and induction of oxidative stress limit their use [4,5]. Thus, discovering molecules that deliver NO• over longer periods is an exciting challenge. Among them, S-nitrosoglutathione (GSNO), displaying limited toxicity is a physiological reservoir of NO• and has been considered for therapeutic use [6]. Many studies have evaluated its therapeutic efficacy in cardiovascular diseases and cancer [7]. Besides, GSNO has been tested as an anti-fungal agent by topical administration [8]. Nevertheless its short half-life, 45 min to 2 h [9], impairs its use in clinical trials. Indeed, GSNO half-life depends primarily on the presence of GSNO reductase (GSNOR), an enzyme which catalyzes the breakdown of GSNO to glutathione disulfide (GSSG) and ammonia (NH3) in the present of glutathion (GSH) [10]. Therefore, unlike other GSNO metabolizing enzymes, the end product of the GSNOR catalyzed reaction is not NO•. As a result, GSNOR removes NO• from the total available pool in the cell. So, GSNOR decreases the bioavailability of NO•, hence the interest of the development of inhibitors of this enzyme [11]. Other non-enzymatic factors can certainly play a role in the GSNO metabolism such as Cu/Fe anions [12], pH and temperature [13]. In addition, it has been shown that GSNO decomposes homolytically producing thiol (GS•) and NO• radicals, or heterolytically by producing NO+ or NO− [14,15].