Superoxide Dismutase (SOD) and the Paf-Antagonist (BN 52021) Reduce Small Intestinal Damage Induced by Ischemia-Reperfusion

Droy-Lefaix, Marie-Thérèse; Drouet, Yvette; Géraud, Gérard; Hosford, David; Braquet, P.

doi:10.3109/10715769109145852

Cited by 79 publications

(40 citation statements)

References 15 publications

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“…Likewise, the generation of the pro-ulcerogenic mediator, thromboxane A2 (Whittle, 1993) by neutrophils, platelets or local tissue in the mucosal injury caused by NO donors can be excluded because of the lack of effect of the thromboxane synthase inhibitor, OKY 1581. Since both PAF and neutrophils play an important role in injury following ischameiareperfusion injury in the stomach and intestine (Grisham et al, 1986;Morgan-Smith et al, 1987;Wallace et al, 1990;Droy-Lefaix et al, 1991), these present findings also suggest that NO-donor provoked gastric damage is not a result of similar ischaemic events in the mucosal microcirculation.…”

Section: Effects Of Anti-neutrophil Serumsupporting

confidence: 61%

Involvement of superoxide and xanthine oxidase in neutrophil‐independent rat gastric damage induced by NO donors

Lamarque

Whittle

1995

British J Pharmacology

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1 Nitric oxide (NO) and the superoxide anion can interact to form the cytotoxic moiety, peroxynitrite. The involvement and potential source of superoxide in the gastric mucosal damage induced by local infusion of NO donors, has now been investigated in the pentobarbitone-anaesthetized rat.2 Local intra-arterial infusion of the NO donor, sodium nitroprusside (40 ,g kg-' min-) for 10 min induced macroscopically apparent gastric mucosal injury. 3 This mucosal damage was dose-dependently reduced by prior administration of a systemically acting form of superoxide dismutase conjugated with polyethylene glycol (500-2000 iu kg-', i.v.).4 Likewise, the mucosal damage induced by nitroprusside was dose-dependently reduced by prior administration of the xanthine oxidase inhibitor, allopurinol (20-100 mg kg-, i.p. or 100 mg kg-, p.o.). 5 Pretreatment with allopurinol (100 mg kg-', i.p.) also reduced the mucosal injury induced by local intra-arterial infusion of the nitrosothiol, S-nitroso-N-acetyl-penicillamine (40 jg kg-' min-), but not that induced by local infusion of endothelin-1 (5 pmol kg-min-'), indicating specificity of action.6 Prior administration (4h) of rabbit anti-rat neutrophil serum (0.4 ml kg-, i.p.), which reduced circulating neutrophils by 90%, did not significantly protect against mucosal injury induced by nitroprusside.7 Intravenous administration of the platelet-activating factor receptor antagonists, WEB 2086 (1 mg kg-') or BN 52021 (10 mg kg-), or the thromboxane synthase inhibitor, OKY 15181 (25 mg kg-), did not modify mucosal damage induced by nitroprusside, showing lack of involvement of these neutrophilderived mediators. 8 These findings indicate the involvement of superoxide in the injurious actions of the NO donors, implicating a cytotoxic role of peroxynitrite. Xanthine oxidase, but not neutrophils, appears to be a source of the superoxide.

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Section: Effects Of Anti-neutrophil Serumsupporting

confidence: 61%

Involvement of superoxide and xanthine oxidase in neutrophil‐independent rat gastric damage induced by NO donors

Lamarque

Whittle

1995

British J Pharmacology

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“…The role of O 2 Ϫ in the inflammatory response was suggested in the 1970s by McCord and Fridovich. 22 Important proinflammatory roles for O 2 Ϫ include endothelial cell damage and increased microvascular permeability, 23 lipid peroxidation and oxidation, DNA single-strand damage, 24 and formation of peroxynitrate. 8,25 Presently, there is no method available to assess directly O 2 Ϫ formation in vivo in humans.…”

Section: Discussionmentioning

confidence: 99%

High Doses of Vitamin C Reverse Escherichia coli Endotoxin–Induced Hyporeactivity to Acetylcholine in the Human Forearm

et al. 2002

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Background-Acute inflammation causes endothelial vasodilator dysfunction that may be mediated by oxidative stress. Methods and Results-In this randomized, double-blind, crossover study, forearm blood flow responses to acetylcholine (ACh) (endothelium-dependent dilator) and glyceryl-trinitrate (GTN) (endothelium-independent dilator) were assessed before and after induction of acute systemic inflammation by low doses of Escherichia coli endotoxin (LPS) (20 IU/kg IV) in 8 healthy volunteers. The acute effect of intra-arterial vitamin C (24 mg/min) or placebo was studied 4 hours after LPS, respectively. Vitamin C alone was administered in control experiments. LPS administration caused systemic vasodilation, increased white blood count, elevated body temperature, and reduced vitamin C plasma concentrations. LPS decreased the responses of forearm blood flow to ACh by 30% (PϽ0.05) but not to GTN. Vitamin C completely restored the response to ACh, which was comparable with that observed under baseline conditions. Vitamin C had no effect on basal blood flow or ACh-or GTN-induced vasodilation in control subjects. Conclusions-Our data demonstrate that impaired endothelial vasodilation caused by E coli endotoxemia can be counteracted by high doses of antioxidants in vivo. Oxidative stress may play an important role in the pathogenesis of endothelial dysfunction during inflammation.

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“…Such an imbalance results in superoxide-mediated injury, as shown in numerous animal models of disease (Fridovich, 1999;Muscoli et al, 2003). Important proinflammatory roles for superoxide include endothelial cell damage and increased microvascular permeability (Droy-Lefaix et al, 1991), release of cytokines (Salvemini et al, 1999;Matata and Galinanes, 2002), recruitment of neutrophils at sites of inflammation (Boughton-Smith et al, 1993;Salvemini et al, 1999), single-strand DNA damage (Dix et al, 1996), and poly-ADP-ribose-polymerase (PARP) activation (Inoue and Kawanishi, 1995). Furthermore, superoxide rapidly combines with nitric oxide (NO), removing an important homeostatic signaling molecule and at the same time forming peroxynitrite, a potent cytotoxic and proinflammatory agent (Beckman et al, 1990).…”

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confidence: 99%

A Newly Identified Role for Superoxide in Inflammatory Pain

Wang¹,

Porreca

Cuzzocrea

et al. 2004

J Pharmacol Exp Ther

350

361

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Novel classes of pain-relieving molecules are needed to fill the void between nonsteroidal anti-inflammatory agents and narcotics. Our studies have identified superoxide as a novel mediator of hyperalgesia (clinically defined as an augmented sensitivity to painful stimuli) and have exposed potential pathways through which this radical modulates the hyperalgesic response. The role of superoxide in pain was elucidated using a superoxide dismutase mimetic, M40403 [a manganese(II) complex with a bis(cyclo-hexylpyridine-substituted) macrocyclic ligand]. Intraplantar injection of carrageenan in rats led to timedependent development of peripheral inflammation [measured parameters of inflammation included paw edema, cytokine release in the paw exudates, nitrotyrosine formation (a marker of peroxynitrite formation and oxidative stress), and poly-ADPribose-polymerase activation (the nuclear enzyme activated by superoxide/peroxynitrite)] and hyperalgesia. M40403 blocked all measured parameters of inflammation and hyperalgesia. Furthermore, when given therapeutically (2 h after the induction of hyperalgesia) either by intravenous or intrathecal administration, M40403 but not its inactive congener M40404 inhibited hyperalgesia with a rapid onset of action. Our results also show that, at the level of the spinal cord and time of peak hyperalgesia, endogenous manganese superoxide dismutase was nitrated and subsequently deactivated, losing its capacity to remove superoxide. The antihyperalgesic effects of M40403 were not reversed by naloxone excluding the potential involvement of an opiate pathway. Collectively, these studies have unraveled a critical role for superoxide in the nociceptive signaling cascade both peripherally and centrally. The discovery of this pathway opens a new therapeutic strategy for the development of novel nonnarcotic antihyperalgesic agents.

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Superoxide Dismutase (SOD) and the Paf-Antagonist (BN 52021) Reduce Small Intestinal Damage Induced by Ischemia-Reperfusion

Cited by 79 publications

References 15 publications

Involvement of superoxide and xanthine oxidase in neutrophil‐independent rat gastric damage induced by NO donors

Involvement of superoxide and xanthine oxidase in neutrophil‐independent rat gastric damage induced by NO donors

High Doses of Vitamin C Reverse Escherichia coli Endotoxin–Induced Hyporeactivity to Acetylcholine in the Human Forearm

A Newly Identified Role for Superoxide in Inflammatory Pain

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