Blood-Clotting Response Test for Bromadiolone Resistance in Norway Rats

Gill, J. E.; Kerins, Gerard M.; Langton, S. D.; MacNicoll, Alan

doi:10.2307/3809316

Cited by 39 publications

(39 citation statements)

References 10 publications

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“…For R. norvegicus, an animal is considered to be susceptible if, after a specified period of dosing, its plasma PCA is less than 17% (Martin et al, 1979;MacNicoll and Gill, 1993;Prescott and Buckle, 2000) or 10% (Gill et al, 1994;Gill et al, 1993). In this rat species, PCA of 17% corresponded approximately with an INR of 5 using Diagen rabbit brain thromboplastin reagent (Prescott et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

“…Though laboratory feeding tests with anticoagulant bait are the final proof of resistance, but procedures are slow, unhumane and labour intensive (Prescott et al, 2007). The BCR tests have several advantages over feeding tests (Gill et al, 1994). They are more quickly performed, are considered to be more humane and are independent of the feeding behaviour of animals.…”

Section: Introductionmentioning

confidence: 99%

“…Later BCR tests were based on the methodology of OEEP/EPPO (1999), where a discriminating dose was calculated that would make susceptible animals respond; failure to respond was taken as evidence of resistance. BCR test methods are available for warfarin (Martin et al, 1979;MacNicoll and Gill, 1993) and second-generation anticoagulants such as difenacoum, bromadiolone, chlorophacinone and diphacinone 1994;Prescott and Buckle, 2000) for few rodent species like Rattus norvegicus and Mus domesticus. For these species, it was proposed that an International Normalised Ratio (INR) equal to or greater than 5 be used as the response in the BCR resistance test (Prescott and Buckle, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Blood clotting response test for detecting resistance to second generation anticoagulant bromadiolone in house rat (Rattus rattus)

Garg¹,

Singla²

2015

IJAR

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Blood clotting response (BCR) test is a faster method with fewer ethical constraints than feed-testing and is widely used to monitor resistance. The second-generation anticoagulant, bromadiolone is being used to control rodents all over India for the last several years. To investigate whether its use has resulted in development of resistance in house rat, Rattus rattus, BCR test was standardized. Plasma samples of 15 rats of both the sexes were pooled separately and diluted with phosphatebuffered saline (pH 7.4). Ten different dilutions of plasma i.e. 4, 5, 6, 8, 10, 20, 40, 60, 80, 100% were tested for Prothrombin Time (PT) and International Normalized Ratio (INR) using rabbit brain thromboplastin reagent in coagulation analyzer. Time to clotting was converted into percent clotting activity (PCA) relative to plasma dilutions, to plot a standard curve. The PT of 15.7 and 17.6 sec for 100% plasma corresponded to INR of 0.8 and 0.9 in male and female rats, respectively. PCA of 22.3% corresponded with PT and INR of 70.3 sec and 3.8, respectively in male rats and PCA of 27.6% corresponded with PT and INR of 63.6 sec and 3.5, respectively in female rats. Data for PT and INR and standard curve for PCA vs PT prepared during present study can be further used to determine current status of bromadiolone resistance in R. rattus populations based on discriminating dose of bromadiolone.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blood clotting response test for detecting resistance to second generation anticoagulant bromadiolone in house rat (Rattus rattus)

Garg¹,

Singla²

2015

IJAR

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“…The aim of this monitoring is to avoid VKA adverse event and to follow possible change in patient physiology (hepatic induction). The purpose of the monitoring of parameters in rodent research is to test VKA molecules or rodent resistance strains [9,10]. They were standardized by the Rodenticide…”

Section: Assessmentmentioning

confidence: 99%

“…These challenges were quite long (many days) and have many shortcomings concerning the animal welfare and the repeatability. Later, new methods based on blood clotting response tests -i.e., 3 the prothrombin time (PT), have been developed [9][10][11]. This new method reduce the experimentation time to 24 h, but is associated with major issues -i.e., the reproducibility and the repeatability of the test.…”

Section: Introductionmentioning

confidence: 99%

Monitoring of antivitamin K-dependent anticoagulation in rodents – Towards an evolution of the methodology to detect resistance in rodents

Lefebvre

Hascoët

Damin-Pernik

et al. 2017

Pesticide Biochemistry and Physiology

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Vitamin K antagonists are used as rodenticides for pest control management. In rodents, prothrombin time is used to monitor their effect despite its limits and the emergence of many coagulation methods. The aim of this study is to explore different coagulation monitoring methods in order to propose the best method and the best parameter to monitor vitamin K antagonists effect in rodents.The coagulation function was thus monitored with global coagulation assays and specialty assays after difethialone administration in rats.Despite many parameters obtained by thromboelastometry, only clotting time and clot formation time obtained by ExTEM were modified. Their evolution was fast with doubling time 1 respectively of 4.0h and 3.7h but their increases were delayed with a lag time higher than 8h.Conversely, prothrombin time evolution presented a lag time of only 2h, but a higher doubling time of 7.2h. The measurements of factor VII and X activities were the most sensitive assays to monitor vitamin K antagonists effect with almost no lag time and the fastest evolution.Nevertheless, factor X was shown to be the only key factor driving prothrombin time.Monitoring factor X activity enables to follow most effectively the anticoagulation status in rats after rodenticides administration.

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Characterization of bromadiolone resistance in a danish strain of Norway rats, rattus norvegicus, by hepatic gene expression profiling of genes involved in vitamin k‐dependent γ‐carboxylation

Markussen

Heiberg

Fredholm

et al. 2007

J Biochem & Molecular Tox

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The present study characterizes the anticoagulant resistance mechanism in a Danish bromadiolone-resistant strain of Norway rats (Rattus norvegicus), with a Y139C VKORC1 mutation. We compared liver expression of the VKORC1 gene, which encodes a protein of the vitamin K 2,3-epoxide reductase complex, the NQO1 gene, which encodes a NAD(P)H quinone dehydrogenase and the Calumenin gene between bromadiolone-resistant and anticoagulant-susceptible rats upon saline and bromadiolone administration. Additionally, we established the effect of bromadiolone on the gene expression in the resistant and susceptible phenotype. Bromadiolone had no effect on VKORC1 and NQO1 expression in resistant rats, but induced significantly Calumenin expression in the susceptible rats. Calumenin expression was similar between the resistant and the susceptible rats upon saline administration but twofold lower in resistant rats after bromadiolone treatment. These results indicate that Danish bromadiolone resistance does not involve an overexpression of calumenin. Independent of the treatment, we observed a low VKORC1 expression in resistant rats, which in conjugation with the Y139C polymorphism most likely explains the low VKOR activity and the enhanced need for vitamin K observed in Danish resistant rats. Furthermore the bromadiolone resistance was found to be associated with a low expression of the NQO1 gene.

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Blood-Clotting Response Test for Bromadiolone Resistance in Norway Rats

Cited by 39 publications

References 10 publications

Blood clotting response test for detecting resistance to second generation anticoagulant bromadiolone in house rat (Rattus rattus)

Blood clotting response test for detecting resistance to second generation anticoagulant bromadiolone in house rat (Rattus rattus)

Monitoring of antivitamin K-dependent anticoagulation in rodents – Towards an evolution of the methodology to detect resistance in rodents

Characterization of bromadiolone resistance in a danish strain of Norway rats, rattus norvegicus, by hepatic gene expression profiling of genes involved in vitamin k‐dependent γ‐carboxylation

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