Water-soluble CO-releasing molecules reduce the development of postoperative ileus via modulation of MAPK/HO-1 signalling and reduction of oxidative stress

Backer, Ole De; Elinck, Ellen; Blanckaert, B; Leybaert, Luc; Motterlini, Roberto; Lefebvre, Romain

doi:10.1136/gut.2008.155481

Cited by 111 publications

(118 citation statements)

References 56 publications

(63 reference statements)

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“…In other in vitro and in vivo investigations involving either mice or rats [24][25][26][27], COHb concentrations varied following CORM exposure, with little increase seen with CORMs that release CO quickly (e.g., CORM-3, tricarbonyldichloro(glycinato)ruthenium (II)), contrasted with COHb values between 8% to 17% after exposure to slow releasing CORMs (e.g., CORM-A1, sodium boranocarbonate, Na 2 [H 3 BCO 2 ]). In sum, when exposed to CO at low or high concentrations (based on COHb), platelet function and measures of intravascular thrombus formation were decreased in mice and rats [18][19][20][21][22][23].…”

Section: Clinical Preclinical and In Vitro Evidence That Co Is An Anmentioning

confidence: 99%

Carbon monoxide: Anticoagulant or procoagulant?

Nielsen

Pretorius

2014

Thrombosis Research

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Within the past decade there have been several investigations attempting to define the impact of exogenous and endogenous carbon monoxide exposure on hemostasis.Critically, two bodies of literature have emerged, with carbon monoxide mediated platelet inhibition cited as a cause of in vitro human and in vitro/in vivo rodent anticoagulation. In contrast, interaction with heme groups associated with fibrinogen, α 2 -antiplasmin and plasmin by carbon monoxide has resulted in enhanced coagulation and decreased fibrinolysis in vitro in human and other species, and in vivo in rabbits. Of interest, the ultrastructure of platelet rich plasma thrombi demonstrates an abnormal increase in fine fiber formation and matting that are obtained from humans exposed to carbon monoxide.Further, thrombi obtained from humans and rabbits have very similar ultrastructures, whereas mice and rats have more fine fibers and matting present. In sum, there may be

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Section: Clinical Preclinical and In Vitro Evidence That Co Is An Anmentioning

confidence: 99%

Carbon monoxide: Anticoagulant or procoagulant?

Nielsen

Pretorius

2014

Thrombosis Research

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“…The water soluble CO-RMs (CORM-3 and CORM-A1) [20,21] have gained increasing interest recently due to their promising pharmacological properties as carriers of therapeutic doses of CO in models of disease including gastrointestinal disorders [22,23]. Indeed, in a murine model of postoperative ileus, we have shown that the "fast" CO releaser CORM-3 markedly reduced 6 the manipulation-induced inflammation of the muscularis and improved surgically induced intestinal dysmotility. This was accompanied by reduction of the early oxidative burst in the mucosa [6].…”

Section: Introductionmentioning

confidence: 88%

“…Notably, in a mouse model of postoperative ileus we recently reported an early and transient increase in oxidative stress in the mucosal layer, with a peak value at 1 h after intestinal manipulation, preceding the peak in the muscularis [6]. The combination of oxidative stressinduced epithelial cell damage, increased intestinal permeability and translocation of intraluminal endotoxins might trigger the muscular inflammation [7]; TNF-α may play a role 5 in this epithelial distress.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, in a murine model of postoperative ileus, we have shown that the "fast" CO releaser CORM-3 markedly reduced 6 the manipulation-induced inflammation of the muscularis and improved surgically induced intestinal dysmotility. This was accompanied by reduction of the early oxidative burst in the mucosa [6]. The second aim of our present study was therefore to investigate the influence of HO-1-related products (bilirubin, biliverdin and CO-RMs) on the oxidative/apoptotic response of the MODE-K cell line to TNF-α/CHX.…”

Section: Introductionmentioning

confidence: 99%

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TNF-α/Cycloheximide-Induced Oxidative Stress and Apoptosis in Murine Intestinal Epithelial MODE-K Cells

Babu

Soenen²,

Raemdonck³

et al. 2012

CPD

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In the mouse postoperative ileus model, we have shown an increase in oxidative stress after intestinal manipulation occurring earlier in the mucosa than in the muscular layer, which might contribute to epithelial barrier dysfunction. To address these findings in vitro, we assessed TNF-α/cycloheximide (CHX)-induced oxidative stress and apoptosis in a mouse intestinal epithelial cell line, MODE-K. The influence of heme oxygenase (HO)-1-related products and agents known to reduce reactive oxygen species (ROS) production on TNF-α/CHX-induced oxidative stress and apoptosis were investigated. MODE-K cells were exposed to different concentrations of TNF-α/CHX in the absence/presence of the test agents.Cell viability, caspase-3/7 activity, apoptosis, reduced glutathione level (GSH) and intracellular ROS production were measured. TNF-α/CHX decreased cell viability, increased caspase-3/7 activity, induced apoptosis, reduced the GSH level and increased ROS production in a concentration-dependent manner in MODE-K cells. All these effects of TNF-α/CHX were partially prevented by pretreatment with a carbon monoxide-releasing agent (CORM-A1) and nitrite. The antioxidant resveratrol abolished TNF-α/CHX-induced increase in ROS production and caspase-3/7 activity, but apoptosis was only partially prevented. MODE-K cells are sensitive to TNF-α-induced apoptosis in the presence of CHX, which is associated with increased intracellular ROS production and caspase-3/7 activation. The effects were partially mitigated by CORM-A1, nitrite and resveratrol. Thus, these agents could be of potential use in protecting the epithelial barrier against oxidative stress during intestinal ischemia/reperfusion injury.

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“…For instance, the iron may be utilised in haemoglobin synthesis as evident in HMOX1 deficient mice that developed iron deficiency anaemia as a result of low serum iron levels (Poss and Tonegawa 1997;Yachie et al 1999). On the other hand, CO has recently been acknowledged as a second messenger of the anti-inflammation signalling transduction pathways in various tissues that can consequently promote overall anti-apoptotic effect (Maines 1997;Brouard et al, 2002;Micheau and Tschopp, 2003;Arruda et al, 2004;Wegiel et al, 2008;De Backer et al, 2009;Gozzelino et al, 2010).…”

Section: Excretion Glucuronidesmentioning

confidence: 99%

Characterisation of bilirubin metabolic pathway in hepatic mitochondria

Muhsain¹

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Bilirubin (BR), a toxic waste product of degraded haem, is a potent antioxidant at physiological concentrations. To achieve the maximum benefit of BR, its intracellular level needs to be carefully regulated. A system comprising of two enzymes, haem oxygenase-1 (HMOX1) and cytochrome P450 2A5 (CYP2A5) exists in the endoplasmic reticulum (ER), responsible for regulating BR homeostasis. This system is induced in response to oxidative stress. In this thesis, oxidative stress caused accumulation of these enzymes in mitochondria -major producers and targets of reactive oxygen species (ROS) -is demonstrated. To understand the significance of this intracellular targeting, properties of microsomal and mitochondrial BR metabolising enzymes were compared and the capacity of mitochondrial CYP2A5 to oxidise BR in response to oxidative stress is reported.Microsomes and mitochondrial fractions were isolated from liver homogenates of DBA/2J mice, administered with sub-toxic dose of pyrazole, an oxidant stressor. The purity of extracted organelles was determined by analysing the expressions and activities of their respective marker enzymes. HMOX1 and CYP2A5 were significantly increased in microsomes and even more so in mitochondria in response to pyrazole-induced oxidative stress. By contrast, the treatment did not increase either microsomes or mitochondrial Uridine-diphosphate-glucuronosyltransferase 1A1 (UGT1A1), the sole enzyme that catalyses BR elimination through glucuronidation.In response to pyrazole-induced oxidative stress, BR oxidation was enhanced not only in microsomes but also in mitochondria. The reaction in both control and pyrazole treated microsomes were blocked by up to 70% with anti-CYP2A5 antibody. By contrast, no CYP2A5 antibody inhibition on BR oxidation was observed in control mitochondria but was 55% inhibited in treated mitochondria. Antibody against adrenodoxin reductase (AdxR) (a component of mitochondrial monooxygenase system) had no effect on the microsomal BR oxidation, but the reaction was inhibited by up to 50% in mitochondria ii after pyrazole treatment. As in microsomes, the antibody had no effect in control mitochondria.Inhibition study with ascorbic acid -a scavenger of ROS -was undertaken to determine the contribution of ROS to BR oxidation. In control microsomes, a slight inhibition of 5% in BR degradation was noted which was augmented to 22% after pyrazole treatment. The inhibition was 100% in control mitochondria but limited to 50% after pyrazole treatment.Mass spectrometry analysis reveals that in microsomes, biliverdin (BV), the main metabolite of CYP2A5-dependant BR oxidation was formed. Meanwhile, mitochondria produced predominantly dipyrroles, the products of BR scavenging ROS. Pyrazole treatment caused mitochondria to yield relatively similar amount of BV and dipyrroles.Enzyme kinetic analysis showed that mitochondrial and microsomal CYP2A5 have an equally strong affinity towards BR. Additionally, no initiation of apoptosis, as indicated by the absence of cytosolic cytochrome...

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Water-soluble CO-releasing molecules reduce the development of postoperative ileus via modulation of MAPK/HO-1 signalling and reduction of oxidative stress

Cited by 111 publications

References 56 publications

Carbon monoxide: Anticoagulant or procoagulant?

Carbon monoxide: Anticoagulant or procoagulant?

TNF-α/Cycloheximide-Induced Oxidative Stress and Apoptosis in Murine Intestinal Epithelial MODE-K Cells

Characterisation of bilirubin metabolic pathway in hepatic mitochondria

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Water-soluble CO-releasing molecules reduce the development of postoperative ileus via modulation of MAPK/HO-1 signalling and reduction of oxidative stress

Cited by 111 publications

References 56 publications

Carbon monoxide: Anticoagulant or procoagulant?

Carbon monoxide: Anticoagulant or procoagulant?

TNF-&alpha;/Cycloheximide-Induced Oxidative Stress and Apoptosis in Murine Intestinal Epithelial MODE-K Cells

Characterisation of bilirubin metabolic pathway in hepatic mitochondria

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TNF-α/Cycloheximide-Induced Oxidative Stress and Apoptosis in Murine Intestinal Epithelial MODE-K Cells