• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.5
• /
• pp.283-287
• /
• 2003

While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.

• Toxicological Research
• /
• v.11 no.2
• /
• pp.303-308
• /
• 1995

Nitric oxide, a physiological transmitter, is reported to mediate cellular injury in various tissues. Its reactivity to free radical is believed to be one of the reasons for its involvement in cytotoxicity. Menadione, a representative quinone, is cytotoxic to several cell systems including isolated hepatocyte, endothelial cell and red blood cells. Its toxic mechanism is related to oxidative stress, mediated by toxic free radicals. Our previous studies demonstrated that menadione induced cell lysis and increase of oxygen consumption in platelets. It has been reported that platelets have nitric oxide producing enzyme, nitric oxide synthase. Thus, we have investigated to manifest the role of nitric oxide.in menadione-induced cytotoxicity in rat platelets. Menadione induced cytotoxicity in platelets was unaffected by $N^G$-nitro-arginine methyl ester (L-NAME), selective and competitive inhibitor of nitric oxide synthase. We also invesitgated the role of extracellular nitric oxide in menadione-induced cytotoxicity of platelets by addition with sodium nitroprusside (SNP). SNP did not affect platelet cytotoxicity by menadione. These results suggested that nitric oxide which was generated endogeneously or exogeneously might have a negligible role in menadione-induced cytotoxicity in rat platelets.

• The Plant Pathology Journal
• /
• v.29 no.4
• /
• pp.427-434
• /
• 2013

2R,3R-Butanediol, a volatile compound produced by certain rhizobacteria, is involved in induced drought tolerance in Arabidopsis thaliana through mechanisms involving stomatal closure. In this study, we examined the involvement of nitric oxide and hydrogen peroxide in induced drought tolerance, because these are signaling agents in drought stress responses mediated by abscisic acid (ABA). Fluorescence-based assays showed that systemic nitric oxide and hydrogen peroxide production was induced by 2R,3R-butanediol and correlated with expression of genes encoding nitrate reductase and nitric oxide synthase. Co-treatment of 2R,3R-butanediol with an inhibitor of nitrate reductase or an inhibitor of nitric oxide synthase lowered nitric oxide production and lessened induced drought tolerance. Increases in hydrogen peroxide were negated by co-treatment of 2R,3R-butanediol with inhibitors of NADPH oxidase, or peroxidase. These findings support the volatile 2R,3R-butanediol synthesized by certain rhizobacteria is an active player in induction of drought tolerance through mechanisms involving nitric oxide and hydrogen peroxide production.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.4
• /
• pp.511-519
• /
• 1998

This study investigated the role of nitric oxide on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion and its relation to mucus. Nitric oxide synthesis modulators such as L-arginine and $N^G-nitro-L-arginine$ methyl ester, and sodium nitroprusside, a nitric oxide donor, were injected intraperitoneally to the rats 30 min prior to ischemia/reperfusion which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. Lipid peroxide production, the contents of glutathione and mucus, and glutathione peroxidase activities of gastric mucosa were determined. Histological observation of gastric mucosa was performed by using hematoxylin-eosin staining and scanning electron microscopy. The result showed that ischemia/reperfusion increased lipid peroxide production and decreased the contents of glutathione and mucus as well as glutathione peroxidase activities of gastric mucosa. Ischemia/reperfusion induced gastric erosion and gross epithelial disruption of gastric mucosa. Pretreatment of L-arginine, a substrate for nitric oxide synthase, and sodium nitroprusside prevented ischemia/reperfusion-induced alterations of gastric mucosa. However, $N^G-nitro-$ L- arginine methyl ester, a nitric oxide synthase inhibitor, deteriorated oxidative damage induced by ischemia/reperfusion. In conclusion, nitric oxide has an antioxidant defensive role on gastric mucosa by maintaining mucus, glutathione, and glutathione peroxidase of gastric mucosa.

• The Korean Journal of Physiology and Pharmacology
• /
• v.4 no.3
• /
• pp.263-270
• /
• 2000

To evaluate the involvement of nitric oxide production on the endothelium-dependent relaxation in diabetes, we have measured vascular and endothelial function and nitric oxide concentration, and the expression level of endothelial nitric oxide synthase in the streptozotocin-induced diabetic rats. Diabetic rats were induced by the injection of streptozotocin (50 mg/kg i.v.) in the Sprague-Dawley rats. Vasoconstrictor responses to norepinephrine (NE) showed that maximal contraction to norepinephrine $(10^{-5}\;M)$ was significantly enhanced in the aorta of diabetic rats. Endothelium-dependent relaxation induced by acetylcholine was markedly impaired in the aorta of diabetic rats, these responses were little improved by the pretreatment with indomethacin. However, endothelium-independent relaxation induced by nitroprusside was not altered in the diabetic rats. Plasma nitrite and nitrate $(NO_2/_3)$ levels in diabetic rats were significantly lower than in non-diabetic rats. Western blot analysis using a monoclonal antibody against endothelial cell nitric oxide synthase (eNOS) revealed that the protein level was lower in the aorta of diabetic rats than in non-diabetic rats. These data indicate that nitric oxide formation and eNOS expression is reduced in diabetes, and this would, in part, account for the impaired endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

• The Journal of Korean Medicine
• /
• v.19 no.2
• /
• pp.112-124
• /
• 1998

The purpose of this study was to investigate the effect of Brousson etiae fructus (BF) on the urethral nitrite level and the urethral nitric oxide synthase (NOS) activity in streptozotocin (STZ) induced diabetic rats. In vitro, the urethral NOS activity was not noted in the level of Dose of extract prepared from BF. In vivo, the urethral NOS activity was increased in normal rats and STZ induced diabetic rats by dose and term of extract prerared from BF. The the NOS activity decreased in STZ induced diabetic rats was increased as highly as norma1 group by the extract of BF The level of urethral nitrite and glutathione was increased too. But the level of urethral lipid peroxide increased in STZ induced diabetic rats was decreased as lowly as normal group by the extract of BF. In conclusion, the extract of BF can restore erectile dysfunction of STZ induced diabetic rats.

• Toxicological Research
• /
• v.19 no.1
• /
• pp.33-37
• /
• 2003

Asiaticoside has been tested for the ability as an anti-inflammatory drug using lipopolysaccharide (LPS)-stimulated macrophage cell line (RAW 264.7 cell). LPS treatment induced dramatically inducible nitric oxide synthase (iNOS) in RAW cells. However, asiaticoside inhibited LPS-stimulated iNOS induction in a concentration-dependent manner. Especially, higher concentrations (＞50 $\mu\textrm{M}$) of asiaticoside completely blocked iNOS induction. In addition, LPS-stimulated expression of inducible cyclooxygenase (COX-2) and interleukin-1 $\alpha$ (IL-1 $\alpha$) was inhibited by asiaticoside treatment. Asiaticoside up to 50 $\mu\textrm{M}$ still required to inhibit COX-2 and IL-1 $\alpha$ induced by LPS. Consistent with these findings, treatment with asiaticoside suppressed do novo synthesis and cellular accumulation of prostaglandin $E_2$ to a lesser extent, suggesting that asiaticoside blocked the induction as well as the activity of COX-2 These results suggest the possibility that asiaticoside may be effective therapeutic agents for septic shock and other inflammatory diseases.

• Biomedical Science Letters
• /
• v.25 no.2
• /
• pp.196-200
• /
• 2019

Effect of retinoids, i.e., all-trans retinoic acid and 13-cis retinoic acid, on the activity of nitric oxide synthase (NOS) was evaluated in human malignant keratinocytes to examine the possible correlation of retinoids with NOS activities. All-trans retinoic acid and 13-cis retinoic acid did not alter the nitric oxide (NO) production. However, in the presence of lipopolysaccharide (LPS, $1{\mu}g/mL$), they significantly increased NO release in a dose-dependent manner until 48 h at concentrations of $50{\sim}100{\mu}M$. The degree of upregulation of NO by all-trans retinoic acid and 13-cis retinoic acid increased up to 35% and 37%, respectively, compared to that by the control, which demonstrated the upregulation of LPS-inducible nitric oxide synthase (iNOS)-dependent generation of NO as well as showing a crucial link between retinoids-induced activity and NOS. Findings of this study now suggest that the upregulation of LPS-iNOS activity may be associated with modulation of retinoids-induced control of cellular developmental processes, which may produce new therapeutics of retinoids in the complexity of how NO affects human keratinocytes.

• The Journal of Korean Medicine
• /
• v.26 no.4
• /
• pp.152-161
• /
• 2005

The excessive release of proinflammatory products by activated microglia causes neurotoxicity, and this has been implicated in the pathogenesis of neurodegenerative diseases. Harpagophytum procumbens (Pedaliaceae) has been widely used for the treatment of pain and arthritis in the clinical field. In this study, we investigated the effect of Harpagophytum procumbens against lipopolysaccharide-induced inflammation. From the present results, the aqueous extract of Harpagophytum procumbens was shown to suppress prostaglandin-E2 synthesis and nitric oxide production by inhibiting the lipopolysaccharide-stimulated enhancement of cyclooxygenase-2 and inducible nitric oxide synthase expressions in mouse BV2 microglial cells. These results suggest that Harpagophytum procumbens may offer a valuable means of therapy for the treatment of brain inflammatory diseases by attenuating lipopolysaccharide-induced prostaglandin-E2 synthesis and nitric oxide production.

• BMB Reports
• /
• v.41 no.1
• /
• pp.79-85
• /
• 2008

The source of nitric oxide (NO) in plants is unclear and it has been reported NO can be produced by nitric oxide synthase (NOS) like enzymes and by nitrate reductase (NR). Here we used wild-type, Atnos1 mutant and nia1, nia2 NR-deficient mutant plants of Arabidopsis thaliana to investigate the potential source of NO production in response to Verticillium dahliae toxins (VD-toxins). The results revealed that NO production is much higher in wild-type and Atnos1 mutant than in nia1, nia2 NR-deficient mutants. The NR inhibitor had a significant effect on VD-toxins-induced NO production; whereas NOS inhibitor had a slight effect. NR activity was significantly implicated in NO production. The results indicated that as NO was induced in response to VD-toxins in Arabidopsis, the major source was the NR pathway. The production of NOS-system appeared to be secondary.