Plasma from patients exposed to ischemia reperfusion contains clastogenic factors and stimulates the chemiluminescence response of normal leukocytes

Emerit, I; Fabiani, Jean‐Noël; Levy, A.; Ponzio, Olivier; Conti, Marc; Brasme, Bernard; Bienvenu, P; Hatmi, Mohamed

doi:10.1016/0891-5849(95)00025-s

Cited by 17 publications

(5 citation statements)

References 24 publications

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“…The plasma of animals in hemorrhagic and endotoxic shock contains activating factors for various cells of the cardiovascular system, such as circulating leukocytes (2,3). Similar activators have been detected in plasma from patients undergoing cardio-vascular surgery (6,9,10,29). The activating factors are markedly increased during shock states and correlate with diminished survival (4).…”

Section: Introductionmentioning

confidence: 54%

The Pancreas as a Source of Cardiovascular Cell Activating Factors

2000

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Section: Introductionmentioning

confidence: 54%

The Pancreas as a Source of Cardiovascular Cell Activating Factors

2000

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“…No CF was found immediately after unclamping. After 20 minutes, samples from peripheral venous blood were also clastogenic, but less than the simultaneous samples taken in the coronary sinus (Emerit et al 1988 and 1995a). We could also show that the luminol-enhanced chemiluminescence (CL) response of neutrophils from healthy persons was increased when these cells were exposed to CF-containing post-reperfusion samples from patients.…”

Section: Results Obtained With the Cf-testmentioning

confidence: 96%

“…Superoxide is not a direct damaging agent, but an initiator of a series of events leading to the formation of clastogenic materials. Biochemical analysis of CF preparations identified three major classes of endogenous chemical clastogens: (i) lipid peroxidation products derived from arachidonic acid of membranes, and in particular the highly clastogenic aldehyde 4-hydroxynonenal (Emerit et al 1991), (ii) cytokines such as tumor necrosis factor alpha (Emerit et al 1995a), and (iii) unusual nucleotides such as inosine di-and triphosphate (Auclair et al 1994). The clastogenic properties of these components were confirmed with the respective commercial standards.…”

Section: Introductionmentioning

confidence: 99%

Clastogenic Factors as Potential Biomarkers of Increased Superoxide Production

Emerit

2007

Biomark�Insights

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The formation of clastogenic factors (CF) and their damaging effects are mediated by superoxide, since superoxide dismutase is regularly protective. CF are produced via superoxide and stimulate the production of superoxide by monocytes and neutrophils. This results in a selfsustaining and longlasting process of clastogenesis, which may exceed the DNA repair system and ultimately lead to cancer (Emerit, 1994). An increased cancer risk is indeed observed in conditions accompanied by CF formation. These include irradiated persons, patients with chronic inflammatory diseases, HIV-infected persons and the chromosomal breakage syndromes ataxia telangiectasia, Bloom’s syndrome and Fanconi’s anemia. Biochemical analysis has identified lipid peroxidation products, arachidonic acid metabolites, nucleotides of inosine and cytokines, in particular tumor necrosis factor alpha, as the clastogenic and also superoxide stimulating components of CF. Due to their chromosome damaging effects, these oxidants can be detected with classical cytogenetic techniques. Their synergistic action renders the CF-test particularly sensitive for the detection of a pro-oxidant state. Correlations were observed between CF and other biomarkers of oxidative stress such as decreases in total plasma thiols or increases in TBARS or chemiluminescence. Correlations between CF and disease activity, between CF and radiation exposure, suggest the study of CF for monitoring these conditions. CF may also be useful as biochemical markers and intermediate endpoints for the evaluation of promising antioxidant drugs.CF formation represents a link between chronic inflammation and carcinogenesis. Prophylactic use of superoxide scavengers as anticarcinogens is therefore suggested.

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“…The myocardial depressant factor was traced by Dr. Lefer and his colleagues to a pancreatic source [56] and it was found to be a low molecular weight peptide [7] . A similar factor from ischemic patients with carcinogenic activity [31] acts via free radical formation [30] . T‐cell immunosuppression factors generated in endotoxic shock include mediators other than lipopolysaccharide [47] .…”

Section: The Biochemical Identity Of the Inflammatory Mediatorsmentioning

confidence: 99%

A New Hypothesis for Microvascular Inflammation in Shock and Multiorgan Failure: Self‐Digestion by Pancreatic Enzymes

Schmid‐Schönbein

Hugli

2005

Microcirculation

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Shock is accompanied by a severe inflammatory cascade in the microcirculation, the origin of which has been hypothesized in the past to be associated with specific mediators such as endotoxin, oxygen free radicals, nitric oxide, cytokines, and lipid products. But no intervention with clinical effectiveness has been derived from these ideas to date. The authors propose here a new hypothesis suggesting that degradative enzymes, synthesized in the pancreas as part of normal digestion, may play a central role in shock and multiorgan failure. These powerful enzymes have the ability to digest almost every biological material. Self-digestion (i.e. autodegradation) is prevented by compartmentalizing the fully activated degradative enzymes in the intestinal lumen by the mucosal barrier. In shock, maintenance of the mucosal barrier is impaired and it becomes permeable to pancreatic enzymes. Digestive enzymes thereby gain access to the wall of the intestine and initiate self-digestion of submucosal extracellular matrix proteins and interstitial cells. The process leads to generation and release of a host of strong inflammatory mediators. The authors hypothesize that inhibition of pancreatic enzymes in the lumen of tile intestine can serve to attenuate formation of these inflammatory mediators in ischemic tissues following hemorrhagic shock, and consequently prevent cell and tissue injury as well as multiorgan failure.

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Plasma from patients exposed to ischemia reperfusion contains clastogenic factors and stimulates the chemiluminescence response of normal leukocytes

Cited by 17 publications

References 24 publications

The Pancreas as a Source of Cardiovascular Cell Activating Factors

The Pancreas as a Source of Cardiovascular Cell Activating Factors

Clastogenic Factors as Potential Biomarkers of Increased Superoxide Production

A New Hypothesis for Microvascular Inflammation in Shock and Multiorgan Failure: Self‐Digestion by Pancreatic Enzymes

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