Swine models in the design of more effective medical countermeasures against organophosphorus poisoning

Dorandeu, Frédéric; Mikler, John; Thiermann, Horst; Tenn, Catherine; Davidson, Corey; Sawyer, T.W.; Lallement, G.; Worek, Franz

doi:10.1016/j.tox.2006.09.013

Cited by 48 publications

(24 citation statements)

References 166 publications

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“…For in vivo studies, experimental animal models, such as rodents (rat, mouse, guinea pig) or rabbits have been used first (Ballantyne and Marrs, 1992;Liu et al, 1999). More recently, in vivo approaches using the domestic pig have demonstrated a real interest of this model for CWA skin absorption studies (Dorandeu et al, 2007;Hawkins and Reifenrath, 1984;Simon and Maibach, 2000;Amitai et al, 2003;Chilcott et al, 2003Chilcott et al, , 2005bHamilton et al, 2004;Duncan et al, 2002;Van der Schans et al, 2003;Kadar et al, 2003). Nevertheless, the in vivo swine model showed many disadvantages, such as the supply and stabling of a large number of pigs or the handling of these animals.…”

Section: Introductionmentioning

confidence: 99%

Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo

Boudry

Blanck

Cruz

et al. 2008

J of Applied Toxicology

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This study determined and compared the percutaneous penetration and absorption of an organophosphorus (OP) pesticide, parathion (PA), using three experimental skin models: namely the human abdominal- and pig-ear skin in vitro models and the Human Skin grafted onto a nude mouse (HuSki) in vivo model. The percentage of topically applied dose absorbed and the doses present in the stratum corneum and skin were systematically determined at 24 h under similar experimental conditions. The three experimental skin models were first compared. Then, the advantages of the HuSki model for in vivo PA skin absorption studies were evaluated compared with the pig in vivo model previously used by others. Lastly, the relevance of each skin model to predict the permeability of human skin to PA in vivo was assessed by comparing our results with previously published in vivo human volunteer values. It was demonstrated that (a) pig-ear skin is relevant for predicting the in vitro human abdominal skin absorption taking into account a 2-3 times higher skin permeability to PA, (b) using ethanol as the vehicle, the absorption of PA was 4-5 times higher in the HuSki model than in the pig model but supports the usefulness of the HuSki model to easy mass balance studies, (c) both human in vitro and HuSki models closely predict the in vivo human volunteer absorption at 24 h when acetone is used as a vehicle but the HuSki model overcomes the known limitations of in vitro models for studying the fate of PA in the different skin layers after topical application.

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Section: Introductionmentioning

confidence: 99%

Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo

Boudry

Blanck

Cruz

et al. 2008

J of Applied Toxicology

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“…However, studies have shown marked species differences in OP pharmacokinetics/ dynamics and response to treatment. Primate and porcine (13) models are currently considered the most clinically relevant animal models, and therefore data from these species are presented preferentially.…”

Section: Pharmacologymentioning

confidence: 99%

Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

Hulse

Davies

Simpson

et al. 2014

Am J Respir Crit Care Med

149

104

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Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities.

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“…Rat plasma exhibited the highest VX detoxification activity of investigated species, resulting in degradation half-times of 25 min (rat), 180 min (mouse), 300 min (rabbit), 900 min (guinea pig, human) and 1200 min (swine). It may be assumed that VX is degraded by enzymes of the carboxylesterase (CaE) family since rodent plasma with rather high CaE concentrations (rat, mice, rabbit) exhibited a higher degradation activity towards VX [50][51][52]. The kinetics of EA-2192 formation was comparable in plasma of all tested species and in Tris-HCl buffer pH 7.4 indicating that the mechanism was not enzymatic.…”

Section: Accuracy and Precisionmentioning

confidence: 99%

Simultaneous quantification of VX and its toxic metabolite in blood and plasma samples and its application for in vivo and in vitro toxicological studies

Reiter

Mikler

Hill

et al. 2011

Journal of Chromatography B

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Swine models in the design of more effective medical countermeasures against organophosphorus poisoning

Cited by 48 publications

References 166 publications

Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo

Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo

Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

Simultaneous quantification of VX and its toxic metabolite in blood and plasma samples and its application for in vivo and in vitro toxicological studies

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