In vivo biodistribution and oxygenation potential of a new generation of oxygen carrier

Gall, Tony Le; Polard, Valérie; Rousselot, Morgane; Lotte, Auréline; Raouane, Mouna; Lehn, Pierre; Opolon, Paule; Leize, Elisabeth; Deutsch, Éric; Zal, Franck; Montier, Tristan

doi:10.1016/j.jbiotec.2014.07.008

Cited by 33 publications

(51 citation statements)

References 22 publications

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“…It is active over a wide range of temperatures 12 and has a half-life, determined using M101 tagged with fluorescent dye, of age 3 of 39 4 ~24 h in rats. 13 M101 has been shown to improve organ preservation 12,14 and a recent study, measuring arterioles and venules in the hamster dorsal skin fold, reports that M101 does not have vasoconstrictive properties. 10 These product characteristics and pharmacodynamic data make M101 a candidate for further development for pre-hospital treatment for TBI if the product 1) does not cause cerebral arteriolar vasoconstriction (safety) and 2) shows evidence of reducing brain injury (efficacy) in TBI models.…”

Section: Introductionmentioning

confidence: 99%

Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats

Moon-MassatPaula

Habib-E-Rasul

AbutarboushRania

et al. 2017

Journal of Neurotrauma

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The severity of traumatic brain injury (TBI) may be reduced if oxygen can be rapidly provided to the injured brain. This study evaluated if the oxygen-carrier M101 causes vasoconstricton of pial vasculature in healthy rats (Experiment 1) and if M101 improves brain tissue oxygen (PbtO) in rats with controlled cortical impact (CCI)-TBI (Experiment 2). M101 (12.5 mL/kg intravenous [IV] over 2 h) caused a mild (9 mm Hg) increase in the mean arterial blood pressure (MAP) of healthy rats without constriction of cerebral pial arterioles. M101 (12 mL/kg IV over 1 h) caused a modest (27 mm Hg) increase in MAP (peak, 123 ± 5 mm Hg [mean ± standard error of the mean]) of CCI-TBI rats and restored PbtO to near pre-injury levels. In both M101 and untreated control (NON) groups, PbtO was ∼30 ± 2 mm Hg pre-injury and decreased (p ≤ 0.05) to ∼16 ± 2 mm Hg 15 min after CCI. In NON, PbtO remained ∼50% of baseline but M101 administration resulted in a sustained increase in PbtO (peak, 25 ± 5 mm Hg), which was not significantly different from pre-injury until the end of the study, when it decreased again below pre-injury (but was still higher than NON). Histopathology showed no differences between groups. In conclusion, M101 increased systemic blood pressures without concurrent cerebral pial vasoconstriction (in healthy rats) and restored PbtO to 86% of pre-injury for at least 80 min when given soon after CCI-TBI. M101 should be evaluated in a clinically-relevant large animal model for pre-hospital treatment of TBI.

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Section: Introductionmentioning

confidence: 99%

Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats

Moon-MassatPaula

Habib-E-Rasul

AbutarboushRania

et al. 2017

Journal of Neurotrauma

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“…These results are in good agreement with previous observations from Le Gall et al, who used HC tagged with a fluorescent dye to follow its distribution and elimination in vivo in mice. Biofluorescence imaging as well as spectrometry measurements indicated the presence of a functional oxygenated HC‐originated product in plasma up to 6 h post‐injection.…”

Section: Resultsmentioning

confidence: 99%

“…They were stored at ‐80 °C, then thawed at 4 °C before the experiments. Final concentrations (200 mg/kg and lower concentrations) were based on previous studies in mice …”

Section: Methodsmentioning

confidence: 99%

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Application of HBOCs electrophoretic method to detect a new blood substitute derived from the giant extracellular haemoglobin of lugworm

Marchand

Crepin

Roulland

et al. 2017

Drug Testing and Analysis

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Manipulation of blood and blood components is prohibited in sports by the World Anti‐Doping Agency (WADA). This includes the use of blood substitutes to increase oxygen transport, like haemoglobin‐based oxygen carriers (HBOCs), which are compounds derived from haemoglobin. Despite their medical interest, the first generation of HBOCs had serious adverse effects and was abandoned. However, new studies are now exploiting the properties of marine worm haemoglobins, which circulate as giant extracellular complexes with high oxygen‐binding capacities. HEMOXYCarrier® (HC), developed by Hemarina, is one of the most advanced and promising HBOCs, and HC may become a tempting doping tool for athletes in the future. Here, HC detection in plasma/serum was evaluated with the method used to detect the first HBOCs, based on electrophoresis and heme peroxidase properties. An HC‐derived product was identified in human plasma up to 72 h after in vitro incubation at 37 °C. HC degradation also induced methemalbumin formation. After injecting HC at the effective dose of 200 mg/kg into mice, the HC‐derived product was detected only for a few hours and no accumulation of methemalbumin was observed. Due to this limited detection window in vivo, measuring specific worm globin degradation products by mass spectrometry might be an alternative for future anti‐doping analyses. Copyright © 2016 John Wiley & Sons, Ltd.

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“…Recently, an extracellular haemoglobin called M101 (produced by HEMARINA, Morlaix) isolated from the lugworm Arenicola marina , has been developed under the product name of HEMO 2 life ® as an additive to preservation solutions during hypothermic storage of grafts. M101 possesses a high affinity for oxygen and can carry up to 156 oxygen molecules, compared to the four oxygen molecules carried by human haemoglobin . Oxygen release occurs over a gradient without any allosteric effectors, and according to the p50 of the molecule .…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of the novel marine oxygen carrier M101 during cold preservation of rat and human pancreas

Lemaire

Sigrist

Delpy³

et al. 2019

J Cellular Molecular Medi

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Ischaemia impairs organ quality during preservation in a time‐dependent manner, due to a lack of oxygen supply. Its impact on pancreas and islet transplantation outcome has been demonstrated by a correlation between cold ischaemia time and poor islet isolation efficiency. Our goal in the present study was to improve pancreas and islet quality using a novel natural oxygen carrier (M101, 2 g/L), which has been proven safe and efficient in other clinical applications, including kidney transplantation, and for several pre‐clinical transplantation models. When M101 was added to the preservation solution of rat pancreas during ischaemia, a decrease in oxidative stress (ROS), necrosis (HMGB1), and cellular stress pathway (p38 MAPK)activity was observed. Freshly isolated islets had improved function when M101 was injected in the pancreas. Additionally, human pancreases exposed to M101 for 3 hours had an increase in complex 1 mitochondrial activity, as well as activation of AKT activity, a cell survival marker. Insulin secretion was also up‐regulated for isolated islets. In summary, these results demonstrate a positive effect of the oxygen carrier M101 on rat and human pancreas during preservation, with an overall improvement in post‐isolation islet quality.

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In vivo biodistribution and oxygenation potential of a new generation of oxygen carrier

Cited by 33 publications

References 22 publications

Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats

Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats

Application of HBOCs electrophoretic method to detect a new blood substitute derived from the giant extracellular haemoglobin of lugworm

Beneficial effects of the novel marine oxygen carrier M101 during cold preservation of rat and human pancreas

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