ANTIOXIDANT LAZAROID U-74006F IMPROVES RENAL FUNCTION AND REDUCES THE EXPRESSION OF CYTOKINES, INDUCIBLE NITRIC OXIDE SYNTHASE, AND MHC ANTIGENS IN A SYNGENEIC RENAL TRANSPLANT MODEL

1996 ◽  
Vol 62 (11) ◽  
pp. 1628-1633 ◽  
Author(s):  
Abdulla Salahudeen ◽  
Chunyou Wang ◽  
Olga McDaniel ◽  
Sandya Lagoo-Denadyalan ◽  
Steven Bigler ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Function ◽  
Renal Transplant ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Mhc Antigens ◽  
Oxide Synthase ◽  
Transplant Model ◽  
Inducible Nitric Oxide

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

2004 ◽  
Vol 287 (1) ◽  
pp. H209-H215 ◽  
Author(s):  
Bruno Levy ◽  
Chantal Vallée ◽  
Francois Lauzier ◽  
Gérard E. Plante ◽  
Arnaud Mansart ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Function ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Endotoxic Shock ◽  
High Energy ◽  
Selective Inhibitor ◽  
High Energy Phosphates ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Norepinephrine (NE), a standard of care, AVP, an alternative candidate, and l-canavanine (LC), a selective inhibitor of inducible nitric oxide synthase, were compared for efficacy and innocuousness on global and regional hemodynamics, plasmatic and tissue lactate-to-pyruvate ratio (L/P), tissue high-energy phosphates, renal function, and tissue capillary permeability in a rat model of endotoxic normokinetic shock. Mean arterial pressure (MAP) decreased (∼35%) but aortic blood flow increased during endotoxin infusion ( P < 0.05 vs. control). Additionally, there was a decrease in mesenteric (MBF) and renal (RBF) blood flows along with regional-to-systemic ratio ( P < 0.05 vs. control). All tested drugs restored MAP to basal levels but slightly decreased abdominal aortic flow; however, RBF and MBF remained unchanged. Endotoxin significantly decreased diuresis and inulin clearance (∼3- to 4-fold), whereas AVP or LC attenuated this drop ( P < 0.05 vs. control). In contrast, NE did not improve endotoxin-induced renal dysfunction. Endotoxin induced gut and lung hyperpermeability ( P < 0.05 vs. control). Endotoxin-induced gut hyperpermeability was inhibited by AVP, LC, and NE. Endotoxin-induced lung hyperpermeability was further worsened by NE (∼2-fold increase) but not AVP infusion ( P < 0.05 vs. endotoxin). LC significantly improved endotoxin-induced pulmonary hyperpermeability. Endotoxin increased renal lactate and decreased renal ATP. NE did not change renal lactate or renal ATP. AVP and LC decreased renal lactate and normalized renal ATP. Finally, endotoxin was associated with increased lactate levels and L/P (∼2- and 1.5-fold increases vs. control, respectively), whereas AVP and LC, but not NE, normalized both parameters after endotoxin challenge. These results suggest that, in a short-term endotoxic shock model, AVP improves systemic hemodynamics without side effects and has particular beneficial effects on renal function.

289: Roles of Inducible Nitric Oxide Synthase in Voiding Function and Bladder Pain During Experimental Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 96-96
Author(s):  
Masayoshi Nomura ◽  
Hisae Nishii ◽  
Masato Tsutsui ◽  
Naohiro Fujimoto ◽  
Tetsuro Matsumoto
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Voiding Function ◽  
Bladder Pain ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Search for Potential Inducible Nitric Oxide Synthase Inhibitors with Favorable ADMET Profiles for the Therapy of Helicobacter pylori Infections

2020 ◽  
Vol 19 (30) ◽  
pp. 2795-2804 ◽  
Author(s):  
Ricardo Pereira Rodrigues ◽  
Juliana Santa Ardisson ◽  
Rita de Cássia Ribeiro Gonçalves ◽  
Tiago Branquinho Oliveira ◽  
Vinicius Barreto da Silva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Helicobacter Pylori ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Crucial Role ◽  
Chemical Space ◽  
Target Selection ◽  
Oxide Synthase ◽  
Inos Inhibition ◽  
Inducible Nitric Oxide

Background: Helicobacter pylori is a gram-negative bacterium related to chronic gastritis, peptic ulcer and gastric carcinoma. During its infection process, promotes excessive inflammatory response, increasing the release of reactive species and inducing the production of pro-inflammatory mediators. Inducible Nitric Oxide Synthase (iNOS) plays a crucial role in the gastric carcinogenesis process and a key mediator of inflammation and host defense systems, which is expressed in macrophages induced by inflammatory stimuli. In chronic diseases such as Helicobacter pylori infections, the overproduction of NO due to the prolonged induction of iNOS is of major concern. Objective: In this sense, the search for potential iNOS inhibitors is a valuable strategy in the overall process of Helicobacter pylori pathogeny. Method: In silico techniques were applied in the search of interesting compounds against Inducible Nitric Oxide Synthase enzyme in a chemical space of natural products and derivatives from the Analyticon Discovery databases. Results: The five compounds with the best iNOS inhibition profile were selected for activity and toxicity predictions. Compound 9 (CAS 88198-99-6) displayed significant potential for iNOS inhibition, forming hydrogen bonds with residues from the active site and an ionic interaction with heme. This compound also displayed good bioavailability and absence of toxicity/or from its probable metabolites. Conclusion: The top-ranked compounds from the virtual screening workflow show promising results regarding the iNOS inhibition profile. The results evidenced the importance of the ionic bonding during docking selection, playing a crucial role in binding and positioning during ligand-target selection for iNOS.

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