Publications by authors named "Nathalie Priymenko"

16 Publications

  • Page 1 of 1

Relationship between a plant-based 'vegan' pet food and clinical manifestation of multiple nutrient deficiencies in two cats.

J Anim Physiol Anim Nutr (Berl) 2021 Mar 3. Epub 2021 Mar 3.

Nutrition Department, Ecole Nationale Vétérinaire de Toulouse ENVT, Toulouse, France.

A topical subject in human nutrition is the steadily growing number of people choosing to limit or completely avoid all animal-derived food products either for moral dilemma, health concerns or both. To meet people's will of applying their dietary choices to their domestic animals, the pet food industry answered by launching on the market some plant-based diets. This leads to concerns about whether these diets are adequately formulated to satisfy the target species nutritional requirements, especially for cats which are still considered strict carnivores. This case report follows a 2-year-old male neutered Main Coon and a 1-year-old female spayed Domestic Shorthair cat, presented to the nutrition service of the University of Toulouse, France. Reason for consultation was lethargy with in anamnesis a recent dietary transition to a plant-based pet food. Dysorexia, lethargy and muscle waste were present at first consultation. Progressive weight loss developed during follow-ups. A macrocytic, non-regenerative anaemia with serum folates below reference were the main clinical features. Analysis of pet food showed multiple nutrients below minimum recommendation at the average daily intake of both cats. Folic acid supplementation improved dysorexia, and subsequent reintroduction of animal-derived ingredients in the diet restored appetite, weight and a normal mentation in both cases.
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http://dx.doi.org/10.1111/jpn.13510DOI Listing
March 2021

Managing Feline Idiopathic Hypercalcemia With Chia Seeds ( L.): A Case Series.

Front Vet Sci 2020 22;7:421. Epub 2020 Jul 22.

Nutrition Department, École Nationale Vétérinaire de Toulouse, University of Toulouse, Toulouse, France.

We describe for the first time the use of chia seeds ( L.) as a non-pharmacological solution in managing feline idiopathic hypercalcemia when dietary change alone fails. Over a 2-year period of time, three female spayed, middle-aged, Domestic Shorthair cats were diagnosed with idiopathic hypercalcemia. Reason for consultation were lethargy and dysorexia, with a single episode of vomiting described in one cat and dysuria in another. Thorough diagnostic work-up included complete blood count, serum biochemistry, urinalysis, ionized calcium, calcemic hormones, parathyroid hormone-related protein, and imaging of chest and abdomen. Based on different nutritional reasons, each cat was switched to a different high-moisture pet food as first-step in managing the disorder: a high-fiber diet, a diet formulated for chronic kidney disease management and a diet designed to prevent calcium oxalate urolithiasis. In the three cats, 6 weeks of dietary change alone did not result in normocalcemia. Before resorting to any pharmacological solution, supplementation to the diet of chia seeds (2 g/cat/day) was started. After 4 weeks from the introduction of L., all cats achieved normalization of ionized calcium concentration. Chia seeds ( L.) supplementation could be a useful tool in managing feline idiopathic hypercalcemia.
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http://dx.doi.org/10.3389/fvets.2020.00421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387619PMC
July 2020

Dietary regimen of the woodpigeon (Columba palumbus).

J Anim Physiol Anim Nutr (Berl) 2021 Mar 25;105(2):376-384. Epub 2020 Jun 25.

Ecole Nationale Vétérinaire de Toulouse ENVT, Toulouse, France.

Recently, new agricultural policies and European Directives brought to important changes in farming practice, some of which could affect food availability for the wild bird population endangering biodiversity. This study aims to evaluate the consequences of such agricultural changes in France on the woodpigeon's dietary regimen. A total of 1,093 woodpigeons were collected over a four-year period (2014-2017). Voluntary sampling was performed in six regions in the south-west of France by local hunters during this species' autumnal migration and wintering. Ingluvies contents were recovered, macroscopically and microscopically identified, and then weighed before and after drying. Five food groups were identified: acorns, corn, green plant material, cultivated seeds and others. ANOVA testing followed by Tukey's test for multiple comparison were performed (R version 3.5.2). Significance was set at p < .05. A total of 762 woodpigeons met the study's inclusion criteria. Mean weight of total crop contents was less of 9 grams of dry matter. Most frequent food groups were "green plant material" (70.3%), acorns (42.3%) and corn (27.2%). In terms of grams of dry matter, the most important food in the crop content were acorns (62%): these were eaten more during the first two hunting seasons (p < .001), and in region A, lower amount was consumed compared to all other regions. On the contrary, corn intake peaked during the third year (p < .001), and in region A, birds had an increasing intake of this cereal. Cultivated seeds contributed to the diet more during migration (p = .007), while "green plant material" and others more during wintering (p = .011; p = .004). In conclusion, results confirm the opportunistic nature of the woodpigeon, balancing its diet according to food availability. Corn was eaten more in areas where the winter burying of chopped maize stover (mulching), provided by the Nitrate's directive, was in derogation.
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http://dx.doi.org/10.1111/jpn.13409DOI Listing
March 2021

Appetite-stimulating effect of gabapentin vs mirtazapine in healthy cats post-ovariectomy.

J Feline Med Surg 2020 12 28;22(12):1176-1183. Epub 2020 May 28.

Nutrition Department, National Veterinary School of Toulouse (ENVT), Toulouse, France.

Objectives: The aim of the study was to evaluate the appetite-stimulating effect of gabapentin by comparing it with mirtazapine in healthy cats in the first 8 h after ovariectomy surgery.

Methods: This double-masked, placebo-controlled, prospective clinical trial included 60 healthy cats presented to the hospital for ovariectomy: 20 received gabapentin, 21 received mirtazapine and 19 received a placebo immediately before and 6 h after surgery. Food was offered at 2, 4, 6 and 8 h post-ovariectomy. After each meal, food intake was measured. Data were analysed using repeated-measure ANOVA and a linear mixed-model analysis. Post-hoc Tukey's honest significant difference test was performed for multiple comparisons.

Results: Food intake increased in both treatment groups vs placebo. No statistically significant difference was found between cats treated with gabapentin or mirtazapine.

Conclusions And Relevance: Cats receiving gabapentin ate more than cats in the placebo group. Thirty percent of cats in the gabapentin group covered their resting energy requirements, while none of the cats in the placebo group did. Gabapentin and mirtazapine produced similar effects on food intake.
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http://dx.doi.org/10.1177/1098612X20916391DOI Listing
December 2020

Characterization of GMO or glyphosate effects on the composition of maize grain and maize-based diet for rat feeding.

Metabolomics 2018 02 17;14(3):36. Epub 2018 Feb 17.

UMR1332 Biologie du Fruit et Pathologie, INRA, Univ. Bordeaux, Centre INRA de Nouvelle Aquitaine - Bordeaux, 71 av Edouard Bourlaux, 33140, Villenave d'Ornon, France.

Introduction: In addition to classical targeted biochemical analyses, metabolomic analyses seem pertinent to reveal expected as well as unexpected compositional differences between plant genetically modified organisms (GMO) and non-GMO samples. Data previously published in the existing literature led to divergent conclusions on the effect of maize transgenes on grain compositional changes and feeding effects. Therefore, a new study examining field-grown harvested products and feeds derived from them remains useful.

Objectives: Our aim was to use a metabolomics approach to characterize grain and grain-based diet compositional changes for two GMO events, one involving Bacillus thuringiensis toxin to provide insect resistance and the other one conferring herbicide tolerance by detoxification of glyphosate. We also investigated the potential compositional modifications induced by the use of a glyphosate-based herbicide on the transgenic line conferring glyphosate tolerance.

Results: The majority of statistically significant differences in grain composition, evidenced by the use of H-NMR profiling of polar extracts and LC-ESI-QTOF-MS profiling of semi-polar extracts, could be attributed to the combined effect of genotype and environment. In comparison, transgene and glyphosate effects remained limited in grain for the compound families studied. Some but not all compositional changes observed in grain were also detected in grain-based diets formulated for rats.

Conclusion: Only part of the data previously published in the existing literature on maize grains of plants with the same GMO events could be reproduced in our experiment. All spectra have been deposited in a repository freely accessible to the public. Our grain and diet characterization opened the way for an in depth study of the effects of these diets on rat health.
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http://dx.doi.org/10.1007/s11306-018-1329-9DOI Listing
February 2018

In Vivo Study on Analgesic, Muscle-Relaxant, Sedative Activity of Extracts of and In Silico of Certain Compounds Present in This Species.

Biomed Res Int 2018 13;2018:3868070. Epub 2018 May 13.

Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego, CA 92182, USA.

Background: (flatweed) from the family Asteraceae is a medicinal plant found in Europe, Middle East, and India. In folkloric medication, it is used to heal jaundice, dyspepsia, constipation, rheumatism, and hypoglycemia as well as renal problems. Leaves and roots of the plant have antioxidant and antibacterial properties. The plant is a rich source of pharmacologically active phytochemicals; however, it is explored scantily. The objective of the current study was to identify the chemical composition and investigate the biological potency of crude extracts of this plant.

Methods: The crude extract and the fractions were screened for various phytochemical groups of constituents following standard procedures. The acute toxicity was assayed for safe range of dose determination. The analgesic potential of the extract and fractions was assessed by acetic acid-induced writhing test. The muscle-relaxant activity was examined by standard inclined-plane test and traction test. Sedative potential of extract/fractions was assessed by using standard white wood procedures. Furthermore, docking analysis of two compounds present in the ethyl acetate fraction of the plant was assessed against 3D cyclooxygenase-1 and -2 (COX-1 and COX-2).

Results: The extract/fractions of showed significant analgesic effect in model of peripheral algesia. The docking analysis of previously isolated molecules from the plant also exhibited promising interaction with COX-1 and COX-2. Also, the plant has a mild sedative and muscle-relaxant potential. Thus, our study provided pharmacological rationale for the traditional uses of the plant as analgesic and anti-inflammatory remedy.

Conclusion: The crude extracts and fractions exhibited excellent activity due to active phytochemicals. These active phytochemicals also exhibited promising interaction with COX-1 and COX-2. These findings directed researcher to isolate active compounds from which may be used as a potential source of active secondary metabolites.
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http://dx.doi.org/10.1155/2018/3868070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016213PMC
January 2019

A new model for evaluating maintenance energy requirements in dogs: allometric equation from 319 pet dogs.

J Nutr Sci 2017 12;6:e53. Epub 2017 Oct 12.

TOXALIM, Université de Toulouse, Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire de Toulouse (ENVT), 23 chemin des Capelles, BP 87614, 31076 Toulouse cedex, France.

Reports concerning maintenance energy requirements (MER) in dogs are common but most of the data cover laboratory or utility dogs. This study establishes those of healthy adult pet dogs and the factors which cause these energy requirements to vary. Within the framework of a nutrition teaching exercise, each student followed a pet from his entourage and gathered accurate records of its feeding habits. Data have been restricted to healthy adult dogs with an ideal body weight (BW) which did not vary more than 5 % during the study period. A total of 319 eligible records were analysed using multiple linear regression. Variation factors such as ownership, breed, sex and neutered status, bedding location, temperament and feeding habits were then analysed individually using a non-parametric model. Two models result from this study, one excluding age ( 0·813) and a more accurate one which takes into consideration the age in years ( 0·816). The second model was assessed with the main variation factors and shows that: MER (kcal) = × × × × × 128 × BW × age/d ( 0·836), with the effect of the breed, the effect of sex and neutered status, the effect of bedding location, the effect of temperament and the effect of the type of feed. The resulting model is very similar to the recommendations made by the National Research Council (2006) but a greater accuracy was obtained using age raised to a negative power, as demonstrated in human nutrition.
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http://dx.doi.org/10.1017/jns.2017.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672324PMC
October 2017

Evaluation of total body water in canine breeds by single-frequency bioelectrical impedance analysis method: specific equations are needed for accuracy.

BMC Res Notes 2015 Aug 6;8:336. Epub 2015 Aug 6.

Intensive Care Medicine Unit, École Nationale Vétérinaire de Nantes (ONIRIS), Atlanpole La Chantrerie, route de Gachet, CS 40706, 44307, Nantes Cedex 3, France.

Background: Equations based on single-frequency bioelectrical impedance analysis at 50 kHz for determination of total body water content (TBW) have been previously validated in healthy non-sedated beagle dogs. We investigated whether these equations are predictive of TBW in various canine breeds by comparing the results of these equations with TBW values evaluated directly by deuterium oxide (D2O) dilution.

Methods: Total body water content of 13 healthy adult pet dogs of various breeds was determined directly using D2O dilution and indirectly using previous equations based on values obtained with a portable bioelectric impedance device. Paired Student's t-tests were used to compare TBW obtained by single-frequency bioelectrical impedance analysis and D2O dilution. A p-value of <0.05 was considered statistically significant for all analyses.

Results: Significant differences were observed between TBW determined by the reference method and the values obtained with both predictive equations.

Conclusions: The proposed equations including single-frequency bioelectrical impedance analysis parameters validated at 50 kHz in healthy adult beagles need to be modified including morphological parameters such as body size and shape in a first approach. As in humans, morphological-specific equations have to be developed and validated.
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http://dx.doi.org/10.1186/s13104-015-1298-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526165PMC
August 2015

Indirect prediction of total body water content in healthy adult Beagles by single-frequency bioelectrical impedance analysis.

Am J Vet Res 2015 Jun;76(6):547-53

Objective: To develop equations for prediction of total body water (TBW) content in unsedated dogs by combining impedance (resistance and reactance) and morphological variables and to compare the results of those equations with TBW content determined by deuterium dilution (TBW(d)).

Animals: 26 healthy adult Beagles.

Procedures: TBW content was determined directly by deuterium dilution and indirectly with equations developed from measurements obtained by use of a portable bioelectric impedance device and morphological variables including body length, height, weight, and thoracic and abdominal circumferences.

Results: Impedance and morphological data from 16 of the 26 dogs were used to determine coefficients for the following 2 equations: TBW(1) = -0.019 (BL(2)/R) + -0.199 (RC + AC) + 0.996 W + 0.081 H + 12.31; and TBW(2) = 0.048 (BL(2)/R) + -0.144 (RC + AC) + 0.777 W + 0.066 H + 0.031 X + 7.47, where AC is abdominal circumference, H is height, BL is body length, R is resistance, RC is rib cage circumference, W is body weight, and × is reactance. Results for TBW(1) (R(2)(1) = 0.843) and TBW(2) (R(2)(2) = 0.816) were highly correlated with the TBW(d). When the equations were validated with data from the remaining 10 dogs, the respective mean differences between TBW(d) and TBW(1) and TBW(2) were 0.17 and 0.11 L, which equated to a nonsignificant underestimation of TBW content by 2.4% and 1.6%, respectively.

Conclusions And Clinical Relevance: Results indicated that impedance and morphological data can be used to accurately estimate TBW content in adult Beagles. This method of estimating TBW content is less expensive and easier to perform than is measurement of TBW(d), making it appealing for daily use in veterinary practice.
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http://dx.doi.org/10.2460/ajvr.76.6.547DOI Listing
June 2015

Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats.

Free Radic Biol Med 2015 Jun 3;83:192-200. Epub 2015 Mar 3.

UMR 1331 Toxalim, INRA, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.

The end products of polyunsaturated fatty acid (PUFA) peroxidation, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE), and isoprostanes (8-iso-PGF2α), are widely used as systemic lipid oxidation/oxidative stress biomarkers. However, some of these compounds have also a dietary origin. Thus, replacing dietary saturated fat by PUFAs would improve health but could also increase the formation of such compounds, especially in the case of a pro-oxidant/antioxidant imbalanced diet. Hence, the possible impact of dietary fatty acids and pro-oxidant compounds was studied in rats given diets allowing comparison of the effects of heme iron vs. ferric citrate and of ω-6- vs. ω-3-rich oil on the level of lipid peroxidation/oxidative stress biomarkers. Rats given a heme iron-rich diet without PUFA were used as controls. The results obtained have shown that MDA and the major urinary metabolite of HNE (the mercapturic acid of dihydroxynonane, DHN-MA) were highly dependent on the dietary factors tested, while 8-iso-PGF2α was modestly but significantly affected. Intestinal inflammation and tissue fatty acid composition were checked in parallel and could only explain the differences we observed to a limited extent. Thus, the differences in biomarkers were attributed to the formation of lipid oxidation compounds in food or during digestion, their intestinal absorption, and their excretion into urine. Moreover, fecal extracts from the rats fed the heme iron or fish oil diets were highly toxic for immortalized mouse colon cells. Such toxicity can eventually lead to promotion of colorectal carcinogenesis, supporting the epidemiological findings between red meat intake and colorectal cancer risk. Therefore, the analysis of these biomarkers of lipid peroxidation/oxidative stress in urine should be used with caution when dietary factors are not well controlled, while control of their possible dietary intake is needed also because of their pro-inflammatory, toxic, and even cocarcinogenic effects.
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http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.023DOI Listing
June 2015

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse.

Neurotoxicology 2013 Sep 28;38:74-83. Epub 2013 Jun 28.

AgroParisTech, UMR 0791 Modélisation Systémique Appliquée aux Ruminants, F-75005 Paris, France; INRA, UMR 0791 Modélisation Systémique Appliquée aux Ruminants, 16 rue Claude Bernard, F-75005 Paris, France. Electronic address:

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse. C57BL/6J mice orally exposed to 9% H. radicata (HR) are metabolically competent laboratory animals which can be used as model of Australian stringhalt, a neurological horse disease induced by HR ingestion. So, the present study was conducted to assess the brain metabolome and the behavioural performances of mice fed with a 9%-HR-based diet for 21 days. By the end of the period of exposure, mice were investigated for motor activity and coordination, anxiety level, learning and memory performances, social behaviour and rewarding properties of for the plant. Thus, the animals were sacrificed and the brain metabolome was studied using (1)H NMR spectroscopy. HR-exposed mice displayed a motor hyperactivity in several tasks, a less resignation in the forced swimming test, and paradigm place preference for the plant. A bootstrap-based regularized canonical analysis performed on merged behavioural and metabolic datasets showed a clear relationship in HR-treated mice between an increase in cerebral scyllo-inositol, an increased motor activity, and seemingly rewarding properties of HR. These results underlie the interest of such a dual approach to characterize functional end-points of a pathophysiological model of the Australian stringhalt in equine species.
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http://dx.doi.org/10.1016/j.neuro.2013.06.005DOI Listing
September 2013

Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver.

Hepatology 2012 Feb 22;55(2):395-407. Epub 2011 Dec 22.

INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse, France.

Unlabelled: Changes in lifestyle are suspected to have strongly influenced the current obesity epidemic. Based on recent experimental, clinical, and epidemiological work, it has been proposed that some food contaminants may exert damaging effects on endocrine and metabolic functions, thereby promoting obesity and associated metabolic diseases such as nonalcoholic fatty liver disease (NAFLD). In this work, we investigated the effect of one suspicious food contaminant, bisphenol A (BPA), in vivo. We used a transcriptomic approach in male CD1 mice exposed for 28 days to different doses of BPA (0, 5, 50, 500, and 5,000 μg/kg/day) through food contamination. Data analysis revealed a specific impact of low doses of BPA on the hepatic transcriptome, more particularly on genes involved in lipid synthesis. Strikingly, the effect of BPA on the expression of de novo lipogenesis followed a nonmonotonic dose-response curve, with more important effects at lower doses than at the higher dose. In addition to lipogenic enzymes (Acc, Fasn, Scd1), the expression of transcription factors such as liver X Receptor, the sterol regulatory element binding protein-1c, and the carbohydrate responsive element binding protein that govern the expression of lipogenic genes also followed a nonmonotonic dose-response curve in response to BPA. Consistent with an increased fatty acid biosynthesis, determination of fat in the liver showed an accumulation of cholesteryl esters and of triglycerides.

Conclusion: Our work suggests that exposure to low BPA doses may influence de novo fatty acid synthesis through increased expression of lipogenic genes, thereby contributing to hepatic steatosis. Exposure to such contaminants should be carefully examined in the etiology of metabolic diseases such as NAFLD and nonalcoholic steatohepatitis.
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http://dx.doi.org/10.1002/hep.24685DOI Listing
February 2012

Oxidative stress in dog with heart failure: the role of dietary Fatty acids and antioxidants.

Vet Med Int 2011 Apr 6;2011:180206. Epub 2011 Apr 6.

ENVT, 2 allée des Cèdres 66330 Cabestany, France.

In dogs with heart failure, cell oxygenation and cellular metabolism do not work properly, leading to the production of a large amount of free radicals. In the organism, these free radicals are responsible of major cellular damages: this is oxidative stress. However, a suitable food intake plays an important role in limiting this phenomenon: on the one hand, the presence of essential fatty acids in the composition of membranes decreases sensitivity of cells to free radicals and constitutes a first protection against the oxidative stress; on the other hand, coenzyme Q10, vitamin E, and polyphenols are antioxidant molecules which can help cells to neutralize these free radicals.
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http://dx.doi.org/10.4061/2011/180206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087355PMC
April 2011

Cotoneaster sp. poisoning in a llama (Lama glama).

J Vet Diagn Invest 2009 Mar;21(2):247-9

Ecole Nationale Vétérinaire de Toulouse, F-31076 Toulouse, France.

A case of poisoning with a Cotoneaster sp. is described in a llama (Lama glama). The clinical signs were dyspnea, with congested mucous membranes, chewing, recumbency, and opisthotonos. Several hours after ingestion of the plant, the llama died, despite treatment with sodium thiosulfate and nitrite. Necropsy revealed approximately 676 g of leaves and fruit of Cotoneaster in the first compartment of the stomach. The blood was light red and did not clot. Because Cotoneaster sp. contains low concentrations of cyanogenic glycosides, toxicosis occurs only following massive ingestion of plant material.
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http://dx.doi.org/10.1177/104063870902100213DOI Listing
March 2009

Orthologous metabonomic qualification of a rodent model combined with magnetic resonance imaging for an integrated evaluation of the toxicity of Hypochoeris radicata.

Chem Res Toxicol 2008 Nov;21(11):2082-96

UMR 1089 INRA/ENVT, 180 Chemin de Tournefeuille, BP 3, F-31931 Toulouse, France.

In the present study, we have used metabonomics combined with magnetic resonance imaging (MRI) to investigate an orphan neurological disease, Australian stringhalt, described in horse-ingesting inflorescences of Hypochoeris radicata (HR), without any knowledge on the toxic principle and without any practical possibility to perform experiments on the target species. To get valuable candidate biomarkers, we have chosen the mouse species as a "metabolically competent" laboratory animal model. Metabonomics has been applied as a holistic approach to obtain some pertinent metabolic information about the target organs and biomarker metabolites involved in the HR-induced disruptive events. From urine, liver, and brain metabolic fingerprints, HR ingestion induced a very significant effect on the general metabolism, which is proportional to the HR dose administered and to the HR intoxication duration. The main metabolic biomarker in the mouse model of an intoxication specifically induced by HR feeding has been unambiguously identified as scyllo-inositol. A significant increase of this metabolic marker has been measured in urine and in hydrosoluble liver or brain extracts with a very significant canonical link between these two organs. MRI results obtained in the thalamus have confirmed the involvement of scyllo-inositol, a metabolite found in many neurodegenerative diseases, in some specific metabolic disruptions involved in both neuronal and glial dysfunctions as awaited from etiology of this horse disease. This brain metabolic biomarker has been clearly associated with changes in N-acetyl-aspartate, lactate, and choline cerebral concentration found in both neuronal and glial dysfunctions. Scyllo-inositol is a valuable candidate biomarker of the Australian stringhalt disease that needs now to be clinically validated in the target species.
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http://dx.doi.org/10.1021/tx800159xDOI Listing
November 2008

Influence of feeding and analytical method on the bioequivalence of a racemic drug undergoing enantioselective enterohepatic recycling.

J Pharm Sci 2004 Mar;93(3):590-600

Ecole Nationale Vétérinaire de Toulouse, UMR 181 INRA de Physiopathologie et Toxicologie Expérimentales, 23 Chemin des Capelles, 31076 Toulouse Cedex 3, France.

Two crossover bioequivalence trials of an enantioselectively enterohepatic recycled drug, carprofen, were conducted in dogs with the same racemic oral formulation to determine: (i) the influence of feeding patterns, and (ii) the effect of the analytical method (enantioselective vs non-enantioselective) on the statistical power of the trials. The first trial was conducted with a standard feeding protocol and the second with a special feeding protocol selected to ensure constant biliary flow into the duodenum. Using a non-enantioselective technique, 90% confidence intervals provided conclusions of bioequivalence in 100% of the cases for both area under the plasma concentration versus time curve (AUC) and maximum plasma drug concentration (Cmax) with the special feeding protocol, but only 50% for AUC and 13% for Cmax with the standard feeding protocol, suggesting that a feeding pattern that diminishes plasma drug concentration rebound for an enterohepatically recycled drug increases the power of a bioequivalence trial. Whatever the feeding protocol, an enantioselective method decreased the power of the trials for AUC but increased the power of the trials for Cmax. For an enterohepatically recycled drug, feeding pattern can influence the power of a bioequivalence trial, and the analytical technique that provides the greatest power depends on the assessed bioequivalence parameter and the feeding pattern.
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http://dx.doi.org/10.1002/jps.10581DOI Listing
March 2004