Carbon monoxide releasing molecule-3 inhibits concurrent tumor necrosis factor-α- and interleukin-1β-induced expression of adhesion molecules on human gingival fibroblasts

Song, Hui; Zhao, Haiqing; Qu, Yi-Qing; Sun, Qiao; Zhang, F.; Du, Zhenhong; Liang, Wenyi; Yang, Qingqing; Yang, Po‐Min

doi:10.1111/j.1600-0765.2010.01307.x

Cited by 29 publications

(22 citation statements)

References 42 publications

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“…However, studies of the cytotoxic effects of COR-Ms have concentrated on CORM-3, the water-soluble form of CORM-2. Whilst CORM-3 exposure (500 lM; 24 hr) was not indicated to be cytotoxic in human gingival fibroblasts or peripheral blood mononuclear cell studies, as assessed by intracellular LDH release from residual living cells [42], other studies utilising cell quantification assays have shown reduced RAW 264.7 macrophage viability at the same concentration [43]. Our studies utilising the LDH assay to assess cellular toxicity, as detailed above, indicated that CORM-2 interfered with LDH activity and gave unreliable results, hence the subsequent adoption of the CVCA assay.…”

Section: Discussionmentioning

confidence: 95%

Cell Damage Following Carbon Monoxide Releasing Molecule Exposure: Implications for Therapeutic Applications

Winburn

Gunatunga

McKernan

et al. 2012

Basic Clin Pharma Tox

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The cytoprotective properties of carbon monoxide (CO) gas and CO-releasing molecules (CORMs) are well established. Despite promising pre-clinical results, little attention has been paid to the toxicological profile of CORMs. The effects of CORM-2 and its CO-depleted molecule (iCORM-2) (20-400 lM) were compared in primary rat cardiomyocytes and two cell lines [human embryonic kidney (HeK) and Madine-Darby canine kidney Cells (MDCK)]. Cells were assessed for cell viability, apoptosis, necro-sis, cytology, mitochondrial energetics, oxidative stress and cell cycle arrest markers. In separate experiments, the anti-apoptotic effects of CORM-2 and i-CORM-2 treatment were compared against CO gas treatment in HeK and MDCK lines. H 2 O 2-induced cellular damage, measured by lactate dehydrogenase (LDH) release from primary cardiomyocytes, was reduced by 20 lM CORM-2; LDH activity, however, was directly inhibited by 400 lM CORM-2. Both CORM-2/iCORM-2 and CO gas decreased cisplatin-induced caspase-3 activity in MDCK and HeK cells suggesting an anti-apoptotic effect. Conversely, both CORM-2 and iCORM-2 induced significant cellular toxicity in the form of decreased cell viability, abnormal cell cytology, increased apoptosis and necrosis, cell cycle arrest and reduced mitochondrial enzyme activity. Comparison of these markers after CO gas administration to MDCK cells found significantly less cellular toxicity than in 100 lM CORM-2/iCORM-2-treated cells. CO gas did not have an adverse effect on mitochondrial energetics and integrity. Release of CO by low concentrations of intact CORM-2 molecules provides cyto-protective effects. These results show, however, that the ruthenium-based CORM by-product, iCORM-2, is cytotoxic and suggest that the accumulation of iCORM-2 would seriously limit any clinical application of the ruthenium-based CORMs. Carbon monoxide (CO), iron and biliverdin are products of the catabolism of haem by the enzyme haem oxygenase (HO) [1]. Both CO administration and HO-1 induction have been demonstrated to afford cytological and organ protection in a number of models [2,3]. CO provides cytoprotection via a number of different mechanisms that include anti-inflammatory [4], vasodilatory [5,6], anti-coagulative [7], anti-apoptotic [7,8] and anti-proliferative/fibrotic pathways [3]. The anti-apoptotic properties of CO have been demonstrated in both in vivo and in vitro models to involve modulation of intrinsic pathways, extrinsic pathways and also up-regulation of protective anti-apoptotic Bcl-X L /Bax interaction [6-9]. CO exerts a variety of effects on mitochondrial function dependent on its concentration, duration of exposure and cell type studied. Both endogenous and exogenous CO have been demonstrated to diminish cellular respiration via inhibition of complex IV [10,11]. However, inhibition of complex IV by CO may account in part for some of its cytoprotective effects, by creating a 'metabolic hypoxia' [12] and activating anti-inflammatory p38 MAPK pathways via ROS release [13]. Exposure of rats to CO (50 ppm;...

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Section: Discussionmentioning

confidence: 95%

Cell Damage Following Carbon Monoxide Releasing Molecule Exposure: Implications for Therapeutic Applications

Winburn

Gunatunga

McKernan

et al. 2012

Basic Clin Pharma Tox

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“…For example, ruthenium based CO donor CORM-2 was toxic to multiple cell lines (HeK 293 and MDCK) at 100 μM, as was its byproduct after CO release [88]. CORM-3 has shown similar toxicity to RAW 264.7 macrophages, but it is not toxic to human gingival fibroblasts, even at concentrations as high as 500 μM [89,90]. Clearly there remains work to be done to fully understand the toxological profile of ruthenium-based CO donors.…”

Section: Small Moleculesmentioning

confidence: 99%

Gasotransmitter delivery via self-assembling peptides: Treating diseases with natural signaling gases

Qian

Matson

2017

Advanced Drug Delivery Reviews

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“…In particular, CORM-3 [tricarbonylchloro(glycinato)ruthenium(II)] is fully water-soluble, can rapidly liberate CO when dissolved in physiological solutions. In our previous study, we have shown that CORM-3 inhibits the expression of adhesion molecules on human gingival fibroblasts induced by inflammatory cytokines, and reduces the infiltration and adhesion of immunocompetent cells via releasing CO [21]. CORM-3 has been shown to prevent reoccurrence of sepsis, and reduce cecal ligation and puncture-induced liver injury [22,23].…”

Section: Introductionmentioning

confidence: 99%

Carbon Monoxide Releasing Molecule 3 Inhibits Osteoclastogenic Differentiation of RAW264.7 Cells by Heme Oxygenase-1

Pan

Song

Zong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increased osteoclastogenic differentiation may disrupt the balance of bone resorption and formation, giving rise to bone defective disease. The study aimed to investigate the influence of carbon monoxide releasing molecule 3 on osteoclastogenic differentiation of RAW264.7 cells, and explore the possible mechanism underlying the regulatory effect. Methods: Influence of CORM-3 on the proliferation of RAW264.7 cells was determined by CCK-8 assay. RAW264.7 cells were divided into four groups: Control group; Osteoclastogenic differentiation group, in which cells were induced osteoclastogenic differentiation in medium supplemented with 100μg/L RANKL and 50μg/L M-CSF; Degassed CORM-3-osteoclastogenic differentiation group, in which cells were pretreated with 200μmol/L degassed CORM-3 for 6hrs, and then induced osteoclastogenic differentiation; CORM-3-osteoclastogenic differentiation group, in which cells were pretreated with 200μmol/L CORM-3, and then induced osteoclastogenic differentiation. The mRNA and protein expression of RANK, TRAP, MMP-9, Cts-K and HO-1 of the cells during the osteoclastogenic differentiation was checked by RT-qPCR and Western blot. The induced osteoclasts were identified by TRAP staining. The HO-1 expression of the RAW264.7 cells was silenced by lentivirus transfection, and the expression of RANK, TRAP, MMP-9 and Cts-K was examined by RT-qPCR and Western blot. Results: CORM-3 promoted the proliferation of RAW264.7 cells at the concentration of 200μmol/L. Pretreatment with CORM-3, but not degassed CORM-3, significantly decreased the mRNA and protein expression of osteoclast-specific marker TRAP, RANK, MMP-9 and Cts-K induced by RANKL and M-CSF on day 5, 7 and 9 during the osteoclastogenic differentiation (P< 0.05). After HO-1 was silenced by lentivirus transfection, the mRNA and protein expression of TRAP, RANK, MMP-9 and Cts-K in group with CORM-3 pretreatment maintained the same level as in osteoclastogenic differentiation group. Conclusion: CORM-3 inhibits osteoclastogenic differentiation of RAW264.7 cells via releasing CO. The inhibitory effect is mediated partially by HO-1 pathway. The results suggest the potential application of CORM-3 on some bone defective diseases.

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Carbon monoxide releasing molecule-3 inhibits concurrent tumor necrosis factor-α- and interleukin-1β-induced expression of adhesion molecules on human gingival fibroblasts

Abstract: The results of this study bode well for the application of CORM-3 as an anti-inflammatory agent to inhibit NF-κB activity and to suppress the expression of adhesion molecules on HGF, which suggests a promising potential for CORM-3 in the treatment of inflammatory periodontal disease.

Cited by 29 publications

References 42 publications

Cell Damage Following Carbon Monoxide Releasing Molecule Exposure: Implications for Therapeutic Applications

Cell Damage Following Carbon Monoxide Releasing Molecule Exposure: Implications for Therapeutic Applications

Gasotransmitter delivery via self-assembling peptides: Treating diseases with natural signaling gases

Carbon Monoxide Releasing Molecule 3 Inhibits Osteoclastogenic Differentiation of RAW264.7 Cells by Heme Oxygenase-1

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