Maximizing the success of bile duct cannulation studies in rats: recommendations for best practice

Burden, Natalie; Kendrick, John; Knight, L. C.; McGregor, Victoria; Murphy, Helen; Punler, M.J.; Wijk, Hans van

doi:10.1177/0023677217698001

Cited by 9 publications

(6 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bile duct cannulation on Sprague-Dawley (SD) rats was conducted [ 18 ] in a cross-over study design. The freely moving bile duct cannulated rats were kept in metabolic cages.…”

Section: Methodsmentioning

confidence: 99%

In Vitro Stimulation of Multidrug Resistance-Associated Protein 2 Function Is Not Reproduced In Vivo in Rats

et al. 2018

View full text Add to dashboard Cite

Previously we reported that coproporphyrin-I (CP-I) is an optimal probe substrate for multidrug resistance-associated protein 2 (MRP2), and stimulation of MRP2-mediated transport is probe substrate-dependent. In the present investigation, we assessed if the in vitro stimulation is physiologically relevant. Similar to human MRP2 transport, CP-I was transported by rat Mrp2 in a typical Michaelis-Menten kinetics with apparent Km and Vmax values of 15 ± 6 µM and 161 ± 20 pmol/min/mg protein, respectively. In vivo Mrp2 functions were monitored by biliary and renal secretion of CP-I and its isomer CP-III, in bile-duct cannulated rats before and after treatment with mitoxantrone, progesterone, and verapamil. These compounds stimulated Mrp2-mediated CP-I transport in vitro. No significant increase in biliary or renal clearances, as well as in the cumulative amount of CP-I or CP-III eliminated in bile, were detected following treatment with the in vitro stimulators, indicating an in vitro to in vivo disconnect. In presence of 10 µM bilirubin, the in vitro stimulation was suppressed. We concluded that the in vitro stimulation of CP-I transport mediated by Mrp2 is not translatable in vivo, and proposed that the presence of endogenous compounds such as bilirubin in the liver may contribute to the in vitro to in vivo disconnect.

show abstract

“…Bile duct cannulation on Sprague-Dawley (SD) rats was conducted [ 18 ] in a cross-over study design. The freely moving bile duct cannulated rats were kept in metabolic cages.…”

Section: Methodsmentioning

confidence: 99%

In Vitro Stimulation of Multidrug Resistance-Associated Protein 2 Function Is Not Reproduced In Vivo in Rats

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Since rats lack a gall bladder, they are an ideal model for investigating continuous biliary excretion and biotransformation which contributes to understanding of first-pass metabolism. The bile duct cannulation (BDC) model has previously been a focus for collaborative refinements between UK organizations [ 10 ], with a modified tail cuff and cannula system (hereby described as the pin-port model) designed and introduced at Labcorp. This facilitates use of the dual-cannulation method which allows recirculation of bile back into the duodenum during the period following surgical cannulation or wash out periods and simultaneous collection of bile and reinfusion of bile salts following dose administration.…”

Section: Refinements In the Bile Duct Cannulated Rat Model (Lee Crossman)mentioning

confidence: 99%

“…The NC3Rs also directly supports the toxicology community via long-standing collaborations with the Association of British Pharmaceutical Industry (ABPI), European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), other industry consortia and societies or individual companies, with office-led projects and meetings, workshops and conference sessions to investigate opportunities to apply the 3Rs within the different toxicology studies across the sectors. The sharing of data and experience between multiple companies have identified best-practices in processes or procedures that promote refinements such as social housing during telemetry recordings [ 8 ], microsampling for toxicokinetic (TK) blood sampling [ 9 ], multi-faceted improvements to bile duct cannulation studies [ 10 ], and adoption of evident toxicity for acute inhalation toxicity studies [ 11 ]. Some of these topics are expanded further with current industry data in the following sections.…”

Section: Introductionmentioning

confidence: 99%

“…Refinements for surgical procedures: these include the appropriate use of anesthetics and analgesia, procedures or techniques that shorten surgery time or improve success rates, appropriate recovery periods etc. Typical surgical procedures within toxicology studies include implantation of telemetry devices [ 28 ], bile duct cannulations [ 10 ], vascular access ports, or indwelling catheters for repeat intravenous doses or blood samples.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Refining Procedures within Regulatory Toxicology Studies: Improving Animal Welfare and Data

Prior

Blunt²,

Crossman³

et al. 2021

Animals

View full text Add to dashboard Cite

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction with metabolism and toxicity studies using animals. The required studies are outlined within international regulatory guidelines which acknowledge and support the application of the 3Rs to reduce the number of animals used or to refine the procedures performed when these studies are deemed to be necessary. The continued development of new technologies and adoption of best-practice approaches to laboratory animal housing and study procedures has generated a series of refinements that can be incorporated into animal studies throughout the package. These refinements benefit the welfare of fish, mice, rats, rabbits, dogs, minipigs, and non-human primates (NHPs) whilst maintaining or improving data quality within general toxicology, metabolism, and other studies and can also bring efficiencies to processes that benefit study costs and timings. Examples are shared which cover the following topics: social housing of dogs and NHPs, surgical refinements in the rat bile duct cannulation model for collection of data for metabolism studies, whether fasting is really required prior to clinical pathology sampling, and the use of microsampling for toxicokinetics.

show abstract

“…Damage to the bile ducts often poses a serious threat to the patient's life [4,24,26]. In 12-30% of patients operated on for cholecystitis or bile duct damage, scars and, accordingly, scar strictures of the common bile duct are formed in the postoperative period [2]. Therefore, especially many works are devoted to the tactics of surgical treatment of bile duct pathology [3,7,9,34].…”

Section: Introductionmentioning

confidence: 99%

Morphological features of the wall of common bile duct under the conditions of experimental opioid exposure

2020

View full text Add to dashboard Cite

The morphological condition of the bile ducts remains one of the most important problems of modern medical science. In order to obtain an analgesic effect in patients with acute cholangitis, opioids are often used. However, information on the effectiveness of opioids in the treatment of pathological conditions of the bile ducts is contradictory. The rapidly progressive destruction of the intrahepatic bile ducts associated with the use of narcotic agents has been described. Further study of the effect of opioids on the structural organization of the common bile duct is relevant. In order to establish the morphological state of the common bile duct under conditions of long-term opioid exposure, a study was performed on 24 sexually mature white male rats, aged 3.5-5.0 months and weighing 180-200 g, which were injected intramuscularly with Nalbuphine for 6 weeks. The study material is represented by histological specimens of the common bile duct of white rats. The “Aver Media” computer system was used to photograph microspecimens. The “ImageJ” computer program was used to measure the diameter of the lumen and the wall thickness of the common bile duct. After 2 weeks of Nalbuphine administration to white rats, plethora of wall microvessels and a significant increase in the longitudinal diameter of the lumen of the common bile duct were observed. After 4 weeks of the experiment, the common bile duct was dilated, the transverse and longitudinal diameters of its lumen almost doubled, pathological changes in its wall had all the signs of inflammation. In the later stages of the experiment (introduction of Nalbuphine for 6 weeks), the pathological changes increased and manifested by destructuring the wall of the common bile duct, disorganization of cholangiocytes, thinning of the cell layer due to detachment of cholangiocytes, polymorphism of their nuclei, destruction of intercellular junctions, stratification of its own plate, vacuolar dystrophy of the muscular membrane “varicose” expansion of venules, significant smooth muscle hyperplasia of arterioles, the presence of perivascular lymphocytic infiltrates in the duct wall.

show abstract

Maximizing the success of bile duct cannulation studies in rats: recommendations for best practice

Cited by 9 publications

References 4 publications

In Vitro Stimulation of Multidrug Resistance-Associated Protein 2 Function Is Not Reproduced In Vivo in Rats

In Vitro Stimulation of Multidrug Resistance-Associated Protein 2 Function Is Not Reproduced In Vivo in Rats

Refining Procedures within Regulatory Toxicology Studies: Improving Animal Welfare and Data

Morphological features of the wall of common bile duct under the conditions of experimental opioid exposure

Contact Info

Product

Resources

About