Oral or topical administration of L-arginine changes the expression of TGF and iNOS and results in early wounds healing

ABSTRACT PURPOSE: To evaluate the contribution of L-arginine oral or topical rout of administration in the surgical wound healing process. METHODS: L-arginine was orally or topically administrated to mice after a laparotomy model procedure. The wounds were analyzed to evaluate the granulation tissue by HE analysis, collagen deposition, iNOS and cytokines production by immunochemisyry on wound progress. Mice used in this model were healthy, immunosupressed or diabetic and all of them were treated with different concentration of L-arginine and rout of administration. RESULTS: Suggested that groups treated with L-arginine orally or topically improved wound repair when compared with non-treatad mice. L- arginine treatment stimulated TGF-β and restricted NO production leading to a mild Th1 response and collagen deposition in injured area, when it was orally administrated. Topical administration decreased IL-8 and CCR1 expression by wound cells but did not interfere with TNF-α and IL-10 production, ratifying the decrease of inflammatory response, the oral administration however, presented a higher iNOS and TGF-β expression then. L-arginine treatment also improved the improved the wound healing in immunosupressed or diabetic mice. CONCLUSION: L-arginine administrated orally or topically can be considered an important factor in the recuperation of tissues.

Triamcinolone Acetonide Prevents Enhancement of Hypoxia-induced Neuronal and Inducible Nitric Oxide Synthases in the Retinas of Rats with Oxygen-induced Retinopathy

PURPOSE: We investigated whether oxygen-induced retinopathy (OIR) results in changes in the protein expression of neuronal and inducible nitric oxide synthases (nNOS and iNOS, respectively) in rat model of OIR. In addition, we evaluated whether treatment of rats with triamcinolone acetonide (TA) prevents this response. METHODS: To promote OIR, Sprague-Dawley rats were exposed to hyperoxia from postnatal day 2 (P2) to P14. They were then returned to normoxia after P15. TA was injected into the right vitreous of P15 rats, while saline was injected into the left vitreous. At P18 the expression of nNOS and iNOS was determined using Western blotting and immunostaining techniques in retinas obtained from control rats. RESULTS: In P18 OIR rats, the abundance of nNOS and iNOS protein was significantly increased compared with controls. These increases were not observed in the retinas of rats treated with TA. The change in expression of nNOS and iNOS were specific to parvalbumin and glial fibrillary acidic protein-positive cells. Treatment with TA prevented the increased expression of nNOS and iNOS in all samples. CONCLUSIONS: Hypoxia upregulates expression of nNOS and iNOS in OIR rat retinas, which is can be prevented by treatment with TA.

Aging alters the production of iNOS, arginase and cytokines in murine macrophages

The limited amount of information on the primary age-related deficiencies in the innate immune system led us to study the production of inducible nitric oxide synthase (iNOS), arginase, and cytokines in macrophages of young (8 weeks old) and old (72 weeks old) female BALB/c mice. We first evaluated iNOS and arginase inducers on peritoneal (PMΦ) and bone marrow-derived (BMMΦ) macrophages of young BALB/c and C57BL/6 mice, and then investigated their effects on macrophages of old mice. Upon stimulation with lipopolysaccharide (LPS), resident and thioglycolate-elicited PMΦ from young mice presented higher iNOS activity than those from old mice (54.4 percent). However, LPS-stimulated BMMΦ from old mice showed the highest NO levels (50.1 percent). Identical NO levels were produced by PMΦ and BMMΦ of both young and old mice stimulated with interferon-γ. Arginase activity was higher in resident and elicited PMΦ of young mice stimulated with LPS (48.8 and 32.7 percent, respectively) and in resident PMΦ stimulated with interleukin (IL)-4 (64 percent). BMMΦ of old mice, however, showed higher arginase activity after treatment with IL-4 (46.5 percent). In response to LPS, PMΦ from old mice showed the highest levels of IL-1α (772.3 ± 51.9 pg/mL), whereas, those from young mice produced the highest amounts of tumor necrosis factor (TNF)-α (937.2 ± 132.1 pg/mL). Only TNF-α was expressed in LPS-treated BMMΦ, and cells from old mice showed the highest levels of this cytokine (994.1 ± 49.42 pg/mL). Overall, these results suggest that macrophages from young and old mice respond differently to inflammatory stimuli, depending on the source and maturity of the cell donors.

A novel beta-glucan produced by Paenibacillus polymyxa JB115 induces nitric oxide production in RAW264.7 macrophages

The effect of extracellular beta-(1-->3), (1-->6)-glucan, produced by Paenibacillus polymyxa JB115, on nitric oxide (NO) production in RAW264.7 macrophages was investigated. beta-glucan induced the production of NO by RAW264.7 macrophages in a concentration- and time-dependent manner. Moreover, beta-glucan stimulation increased the mRNA expression of iNOS, COX-2 and IL-6 in RAW264.7 macrophages in a concentration-dependent manner.

Effect of sildenafil citrate on interleukin-1beta-induced nitric oxide synthesis and iNOS expression in SW982 cells

The purpose of this study was to identify the effect of sildenafil citrate on IL-1 beta induced nitric oxide (NO) synthesis and iNOS expression in human synovial sarcoma SW982 cells. IL-1 beta stimulated the cells to generate NO in both dose- and time-dependent manners. The IL-1 beta -induced NO synthesis was inhibited by guanylate cyclase (GC) inhibitor, LY83583. When the cells were treated with 8-bromo-cGMP, a hydrolyzable analog of cGMP, NO synthesis was increased upto 5-fold without IL-1 beta treatment suggesting that cGMP is an essential component for increasing the NO synthesis. Synoviocytes and chondrocytes contain strong cGMP phosphodiesterase (PDE) activity, which has biochemical features of PDE5. When SW982 cells were pretreated with sildenafil citrate (Viagra), a PDE5 specific inhibitor, sildenafil citrate significantly inhibited IL-1 beta -induced NO synthesis and iNOS expressions. From this result, we noticed that PDE5 activity is required for IL-1 beta -induced NO synthesis and iNOS expressions in human synovial sarcoma cells, and sildenafil citrate may be able to suppress an inflammatory reaction of synovium through inhibition of NO synthesis and iNOS expression by cytokines.

Celastrol inhibits production of nitric oxideandproinflammatory cytokines through MAPK signal transduction and NF-kappaB in LPS-stimulated BV-2 microglial cells

Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia play an important role in human neurodegenerative disorders. Here, we investigated whether celastrol, which has been used as a potent anti-inflammatory and anti-oxidative agent in Chinese medicine, attenuates excessive production of NO and proinflammatory cytokines such as TNF-alpha and IL-1beta in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-alpha, and IL-1beta in BV-2 cells was largely inhibited in the presence of celastrol, and the attenuation of inducible iNOS and these cytokines resulted from the reduced expression of mRNAs of iNOS and these cytokines, respectively. The molecular mechanisms that underlie celastrol-mediated attenuation were the inhibition of LPS-induced phosphorylation of MAPK/ERK1/2 and the DNA binding activity of NF-kappaB in BV-2 cells. The results indicate that celastrol effectively attenuated NO and proinflammatory cytokine production via the inhibition of ERK1/2 phosphorylation and NF-kappaB activation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders.

El extracto acuoso de viscum album induce la expresión de las sintasas de oxido nítrico inducible y endotelial en corazón aislado y perfundido de cobayo. Evidencia del mecanismo de vasodilatación coronaria / Viscum album aqueous extract induces inducible and endothelial nitric oxide synthases expression in isolated and perfused guinea pig heart. Evidence of the coronary vasodilation mechanism

The pharmacological effect of a Viscum album aqueous extract was evaluated on the Langendorff isolated and perfused heart model in normotense male guinea pig hearts. Coronary vascular resistance, left intraventricular pressure, nitric oxide release in the perfusion liquid, cyclic guanosine monophosphate production, and analysis of inducible and endothelial nitric oxide synthases expression by Western Blot in ventricular tissue were recorded in absence and presence of blockers and inhibitors, such as 3 microM gadolinium chloride, 100 microM N(omega)-nitro-L-arginine methyl ester and 10 microM 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one. V. album aqueous extract exerts a significant decrease in the coronary vascular resistance, which courses with significant increases in nitric oxide and cyclic guanosine monophosphate production. Analysis of the expression of both nitric oxide synthases revealed that this extract significantly induces the expression of both isoforms in guinea pig hearts. These effects were inhibited by the presence of blockers and inhibitors. The coronary vasodilation induced by the extract is mediated by the nitric oxide/soluble guanylyl cyclase pathway. In addition, this extract shows a positive inotropic effect which that is tyramine-mediated by means of beta1-adrenergic stimulation.

A study on the expression of HSP70 and iNOS after human brain contusion / 法医学杂志

OBJECTIVE@#To study the relationship between expression of HSP70, iNOS and traumatic brain contusion (TBI) in different posttraumatic intervals.@*METHODS@#35 samples of brain contusion were examined using immunohistochemecal staining to evaluate the expression of HSP70 and iNOS.@*RESULTS@#Maximal HSP70 expression was found at 0h after brain contusion. The intensity of HSP70 staining decreased remarkably to the minimum at 24h after TBI, then increased gradually. Expression of iNOS positive cells increased significantly and reached the maximum level 48h after TBI, then the expression decreased gradually from the 2nd day to the 11th day.@*CONCLUSION@#The changes of HSP70 and iNOS immunohistochemical staining can be used as a referential data for estimating time interval after human brain contusion.