scholarly journals Cancer Chemopreventive Potential of Humulones and Isohumulones (Hops α- and Iso-α-acids): Induction of NAD(P)H:Quinone Reductase as a Novel Mechanism

2008 ◽  
Vol 3 (12) ◽  
pp. 1934578X0800301 ◽  
Author(s):  
Gregor Bohr ◽  
Karin Klimo ◽  
Josef Zapp ◽  
Hans Becker ◽  
Clarissa Gerhäuser
Keyword(s):  
Nitric Oxide ◽  
Cell Culture ◽  
Animal Models ◽  
Specific Activity ◽  
Oxidation Products ◽  
Phytochemical Analysis ◽  
Inos Activity ◽  
Raw264.7 Cell ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Phytochemical analysis and chemopreventive testing of a special “α-/β-acid free” hops extract led to the identification of isohumulones (hops iso-α-acids) as potent inducers of NAD(P)H:quinone reductase (QR) activity. CD values (concentrations required to double the specific activity of QR in Hepa1c1c7 cell culture) were in the range of 1.3 to 10.2 μg/mL, with CD value of trans-isohumulone < cis-isoadhumulone < cis-isocohumulone < cis-isohumulone (+ trans-isoadhumulone). Humulones (hops α-acids) were equally active with CD values of 3.4 to 7.6 μg/mL. However, these activities were accompanied by cytotoxicity. Cohumulinone and humulinone, oxidation products of co- and n-humulone, were inactive. We further identified isohumulones as potent inhibitors of lipopolysaccharide-induced inducible nitric oxide synthase (iNOS) activity in Raw264.7 cell culture, with IC50 values of 5.9 – 18.4 μg/mL. Humulones and humulinones were inactive at concentrations < 20 μg/mL. These results indicate that isohumulones, which are considered as the most abundant class of polyphenols in beer, should by further investigated for chemopreventive efficacy in animal models.

scholarly journals Effects of chitosan on nitric oxide production and inducible nitric oxide synthase activity and mRNA expression in weaned piglets

2018 ◽  
Vol 60 (No. 8) ◽  
pp. 359-366
Author(s):  
J. Li ◽  
B. Shi ◽  
S. Yan ◽  
L. Jin ◽  
Y. Guo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Inducible Nitric Oxide Synthase ◽  
No Production ◽  
Weaned Piglets ◽  
Inos Activity ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The effects of chitosan on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity and gene expression in vivo or vitro were investigated in weaned piglets. In vivo, 180 weaned piglets were assigned to five dietary treatments with six replicates. The piglets were fed on a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. In vitro, the peripheral blood mononuclear cells (PBMCs) from a weaned piglet were cultured respectively with 0 (control), 40, 80, 160, and 320 &micro;g chitosan/ml medium. Results showed that serum NO concentrations on days 14 and 28 and iNOS activity on day 28 were quadratically improved with increasing chitosan dose (P &lt; 0.05). The iNOS mRNA expressions were linearly or quadratically enhanced in the duodenum on day 28, and were improved quadratically in the jejunum on days 14 and 28 and in the ileum on day 28 (P &lt; 0.01). In vitro, the NO concentrations, iNOS activity, and mRNA expression in unstimulated PBMCs were quadratically enhanced by chitosan, but the improvement of NO concentrations and iNOS activity by chitosan were markedly inhibited by N-(3-[aminomethyl] benzyl) acetamidine (1400w) (P&nbsp;&lt; 0.05). Moreover, the increase of NO concentrations, iNOS activity, and mRNA expression in PBMCs induced by lipopolysaccharide (LPS) were suppressed significantly by chitosan (P &lt; 0.05). The results indicated that the NO concentrations, iNOS activity, and mRNA expression in piglets were increased by feeding chitosan in a dose-dependent manner. In addition, chitosan improved the NO production in unstimulated PBMCs but inhibited its production in LPS-induced cells, which exerted bidirectional regulatory effects on the NO production via modulated iNOS activity and mRNA expression.

scholarly journals Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival

2001 ◽  
Vol 132 (8) ◽  
pp. 1631-1638 ◽  
Author(s):  
Anthony J Kane ◽  
Jane E Barker ◽  
Geraldine M Mitchell ◽  
David R B Theile ◽  
Rosalind Romero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Skin Flap ◽  
Inos Activity ◽  
Flap Survival ◽  
Skin Flap Survival ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Effect of anti—rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes

2001 ◽  
Vol 95 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Metin Tuna ◽  
Sait Polat ◽  
Tahsin Erman ◽  
Faruk Ildan ◽  
A. Iskender Göçer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Tissue ◽  
Inos Activity ◽  
Content Type ◽  
Cord Injury ◽  
Oxide Synthase ◽  
Fine Print ◽  
Inducible Nitric Oxide

Object. The inflammatory cells that accumulate at the damaged site after spinal cord injury (SCI) may secrete interleukin-6 (IL-6), a mediator known to induce the expression of inducible nitric oxide synthase (iNOS). Any increased production of NO by iNOS activity would aggravate the primary neurological damage in SCI. If this mechanism does occur, the direct or indirect effects of IL-6 antagonists on iNOS activity should modulate this secondary injury. In this study, the authors produced spinal cord damage in rats and applied anti—rat IL-6 antibody to neutralize IL-6 bioactivity and to reduce iNOS. They determined the spinal cord tissue activities of Na+-K+/Mg++ adenosine-5′-triphosphatase (ATPase) and superoxide dismutase, evaluated iNOS immunoreactivity, and examined ultrastructural findings to assess the results of this treatment. Methods. Seventy rats were randomly allocated to four groups. Group I (10 rats) were killed to provide normal spinal cord tissue for testing. In Group II 20 rats underwent six-level laminectomy for the effects of total laminectomy alone to be determined. In Group III 20 rats underwent six-level T2–7 laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in the 20 Group IV rats, but these rats also received one (2 µg) intraperitoneal injection of anti—rat IL-6 antibody immediately after the injury and a second dose 24 hours posttrauma. Half of the rats from each of Groups II through IV were killed at 2 hours and the other half at 48 hours posttrauma. The exposed cord segments were immediately removed and processed for analysis. Conclusions. The results showed that neutralizing IL-6 bioactivity with anti—rat IL-6 antibody significantly attenuates iNOS activity and reduces secondary structural changes in damaged rat spinal cord tissue.

Osteopontin inhibits inducible nitric oxide synthase activity in rat vascular tissue

1998 ◽  
Vol 275 (6) ◽  
pp. H2258-H2265 ◽  
Author(s):  
Jeremy A. Scott ◽  
M. Lynn Weir ◽  
Sylvia M. Wilson ◽  
Jim W. Xuan ◽  
Ann F. Chambers ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Vascular Tissue ◽  
Inos Activity ◽  
Inos Protein ◽  
Tissue Levels ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity ◽  
Inducible Nitric Oxide

We tested the hypothesis that osteopontin (OPN) can inhibit the induction of inducible nitric oxide synthase (iNOS) in vascular tissue. iNOS activity was induced in rat thoracic aortas by incubation of the tissue with lipopolysaccharide (LPS) and measured by conversion ofl-[3H]arginine tol-[3H]citrulline. Addition of ≥1 nM recombinant OPN protein significantly reduced the LPS-induced increase in iNOS activity. Western blotting and the RT-PCR were used to determine the effect of LPS with and without OPN on tissue levels of iNOS protein and RNA, respectively. LPS resulted in an increase in iNOS protein and RNA, whereas OPN dose-dependently reduced tissue levels of iNOS activity, protein, and RNA. Mutated OPN proteins, in which the integrin-binding RGD amino acid sequence was deleted or mutated to RGE, resulted in complete and partial loss, respectively, of the ability of OPN to inhibit LPS-induced iNOS activity, implicating integrin binding in the effect. These results indicate that OPN can prevent induction of iNOS in vascular tissue.

scholarly journals Heme Oxygenase-1 Induction Attenuates Inducible Nitric Oxide Synthase Expression and Proteinuria in Glomerulonephritis

1999 ◽  
Vol 10 (12) ◽  
pp. 2540-2550
Author(s):  
PRASUN K. DATTA ◽  
SEVASTI B. KOUKOURITAKI ◽  
KATHLEEN A. HOPP ◽  
ELIAS A. LIANOS
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Heme Oxygenase 1 ◽  
Inos Activity ◽  
Protein Levels ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Abstract. In glomerulonephritis, there is intraglomerular activation of inducible nitric oxide synthase (iNOS) leading to high output production of nitric oxide (NO). This can result in supraphysiologic amounts of NO and cause oxidative injury. It is unknown whether mechanisms of cellular defense against NO-mediated injury exist. Induction of the heme catabolizing enzyme heme oxygenase-1 (HO-1), which generates biliverdin, carbon monoxide (CO), and iron (Fe), may provide such a mechanism, as CO and Fe are two negative modulators of iNOS activity and expression. This study assessed whether upregulation of HO-1 by a specific inducer, hemin, negatively modulates iNOS expression and activity in anti-glomerular basement membrane antibody-mediated glomerulonephritis. Glomerular HO-1 expression in nephritic animals was upregulated by treatment with hemin (30 μmol/kg body wt). iNOS and HO-1 mRNA expression were assessed by reverse transcription-PCR of glomerular total RNA from nephritic animals or nephritic animals pretreated with hemin. iNOS activity in glomeruli was measured by assessing conversion of [14C] L-arginine to [14C] L-citrulline. HO-1 protein levels in glomeruli were assessed by Western blot analysis. The effect of hemin treatment on monocyte/macrophage infiltration was assessed by enumeration of ED-1-positive cells in nephritic glomeruli. iNOS and HO-1 were coinduced in nephritic glomeruli. Hemin treatment of nephritic animals resulted in upregulation of glomerular HO-1 levels and a two- to threefold reduction in glomerular iNOS mRNA levels. iNOS activity in glomeruli was significantly reduced in hemin-treated nephritic animals in which proteinuria was also attenuated without a change in monocyte/macrophage infiltration. Hemin (100 to 200 μM) also reduced iNOS protein levels and enzyme activity in cultured mesangial cells stimulated with cytokines. These studies demonstrate that in glomerular immune injury, hemin treatment upregulates glomerular HO-1 with an attendant downregulation of iNOS expression, and thus points to regulatory interaction between the two systems. The beneficial effect of hemin treatment on proteinuria could be linked to downregulation of iNOS.

scholarly journals Chlamydia trachomatis Persistence in the Female Mouse Genital Tract: Inducible Nitric Oxide Synthase and Infection Outcome

2001 ◽  
Vol 69 (8) ◽  
pp. 5131-5137 ◽  
Author(s):  
Kyle H. Ramsey ◽  
Gurwattan S. Miranpuri ◽  
Ira M. Sigar ◽  
Scott Ouellette ◽  
Gerald I. Byrne
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Chlamydia Trachomatis ◽  
Inducible Nitric Oxide Synthase ◽  
Genital Tract ◽  
Lung Fibroblasts ◽  
Inos Activity ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT It was previously reported that female mice resolve a primaryChlamydia trachomatis urogenital infection independent of inducible nitric oxide synthase (iNOS). We now report that although iNOS-deficient (NOS2−/−) mice resolve culture-apparent infection in a fashion similar to that of normal control (NOS2 +/+) mice, they sustain significantly increased rates of disease, as assessed by hydrosalpinx formation. PCR amplification of ompAfollowed by Southern blot detection of amplicands revealed the presence of chlamydial DNA in the lower genital tracts of both NOS2−/− and NOS2 +/+ mice at ≥120 days postinfection and in upper genital tract tissues at >120 days postinfection. However, only NOS2−/− mice shed low numbers of viable chlamydiae from the lower genital tract after immunosuppressive treatment at 120 days postinfection. When cultured primary murine lung fibroblasts were activated in the presence of gamma interferon (IFN-γ), inhibition of chlamydial growth occurred in both NOS2 +/+ and NOS2−/− cells, but the inhibition was reversible after removal of the cytokine in the NOS2−/− primary cell culture only. The iNOS-independent inhibition was microbistatic but was independent of 2,3-indoleamine dioxygenase activity. We conclude that chlamydial DNA and antigens persist in mice subsequent to culture-apparent resolution. In addition, IFN-γ induces in vivo inhibition of chlamydial growth through microbistatic mechanisms in the absence of iNOS activity, but in the presence of iNOS activity, IFN-γ is microbicidal and effects eradication.

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