The aims of this study were to describe spatial contamination of the environment on a mouflon pasture, as well as to assess the contamination of grass and roots after surface contamination and in depth contamination with feces and buried tissues from animals infected with Mycobacterium avium subsp. paratuberculosis (M. a. paratuberculosis). Samples of soil, roots, and aerial parts of plants were collected from different locations inside the mouflon pasture, and one control sample site was chosen outside the area where the animals are living. M. a. paratuberculosis DNA was present in all the examined sites and was more often detected in roots than in soil. DNA was detected at up to 80 cm of depth and was spatially more widespread than the initial hypothesis of M. a. paratuberculosis leaching vertically into deeper layers of soil. This study broadens our knowledge of the spread and persistence of M. a. paratuberculosis in an environment with highly infected animals.
- MeSH
- krmivo pro zvířata analýza mikrobiologie MeSH
- lipnicovité mikrobiologie MeSH
- Mycobacterium avium subsp. paratuberculosis genetika izolace a purifikace fyziologie MeSH
- nemoci skotu mikrobiologie přenos MeSH
- paratuberkulóza mikrobiologie přenos MeSH
- půda chemie MeSH
- půdní mikrobiologie * MeSH
- skot MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- půda MeSH
Benzimidazoles are frequently and widely used veterinary anthelmintics. Unfortunately, an administration of these anthelmintics does not always result in the expected therapeutic success. Many host-related factors modify pharmacokinetic behavior and efficacy of a chosen anthelmintic. Pharmacokinetics of anthelmintics varies among animals of different species, sex and age. Also diseases, medication, feed and environmental conditions can significantly affect behavior of anthelmintics and resultant drug efficacy in animals. The presented review gathers information, gained in last 20 years, on factors which bring about the variability in performance of benzimidazole anthelmintics in food-producing animals. It is focused particularly on differences in absorption and metabolism of these anthelmintics as these stages of the pharmacokinetic process seem to be the most important for the overall anthelmintic efficacy. The consequences of abnormalities and alterations in pharmacokinetics of benzimidazole anthelmintics are summarized and discussed.
- MeSH
- analýza potravin MeSH
- anthelmintika farmakokinetika MeSH
- benzimidazoly farmakokinetika MeSH
- druhová specificita MeSH
- rezidua léčiv MeSH
- rizikové faktory MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- anthelmintika MeSH
- benzimidazoly MeSH
The aim of this project was to study the influence of haemonchosis, a common parasitic infection of small ruminants caused by Haemonchus contortus, on the activity of biotransformation enzymes and on in vitro flubendazole (FLU) biotransformation in liver and small intestine of lambs (Ovis aries). Twelve lambs were divided into three groups: non-infected animals, animals orally infected with larvae of H. contortus ISE strain for 7 weeks and for 11 weeks. At the end of the experiment, hepatic and intestinal subcellular fractions were prepared and used for assays of biotransformation enzymes activities and FLU metabolism testing. The activities of hepatic cytochromes P450, flavine monooxygenases and carbonyl-reducing enzymes were decreased in infected animals. UDP-glucuronosyl transferase activity was significantly lower (by 35%) in 11 weeks infected animals than that in control animals. When in vitro metabolism of FLU was compared in control and infected animals, significantly lower velocity of FLU reduction was found in infected animals. Slower FLU reduction may be beneficial for the haemonchosis treatment using FLU, because FLU will remain longer in the organism and could cause longer contact of parasites with FLU.
- MeSH
- biotransformace MeSH
- Haemonchus účinky léků MeSH
- hemonchóza farmakoterapie metabolismus veterinární MeSH
- játra enzymologie metabolismus MeSH
- mebendazol analogy a deriváty metabolismus terapeutické užití MeSH
- nemoci ovcí metabolismus MeSH
- ovce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
- Názvy látek
- flubendazole MeSH Prohlížeč
- mebendazol MeSH
Flubendazole (FLU) is indicated for control of helminthoses in pig and avian species (monogastric animals) and its corresponding pharmacokinetics are well known. The information on FLU's pharmacokinetic behavior in animal species with forestomach (ruminants) has been limited although the use of FLU in these species could be beneficial. The aim of this study was to investigate the pharmacokinetics of FLU and its main metabolites in sheep. The effects of animal age (sexually immature and mature ones) and gender were also studied. FLU was orally administered in a single experimental dose (30 mg/kg of body weight) in the form of oral suspension. Treated immature animals (aged 3 months) and 5 months later the same mature individuals (aged 8 months) were kept under the same conditions (food, water and management) and treated with FLU. Within 72 h after FLU administration, plasmatic samples were collected and FLU and its Phase I metabolites were quantified using high-performance liquid chromatography. FLU was detected in very low concentrations only, reduced FLU (FLU-R) was identified as the main metabolite, and hydrolyzed FLU (FLU-H) as the minor one. Formation of FLU-R was stereospecific with (+)-FLU-R domination. The plasmatic concentrations of (+)-FLU-R reached 10-15 times higher values than those of FLU, (-)-FLU-R and FLU-H. A significant gender effect on pharmacokinetics of FLU or (+)-FLU-R metabolite in the mature animals was found and a wide significant difference between lambs and adult sheep in FLU including both metabolites has been proved.
- MeSH
- antinematodní látky krev chemie metabolismus farmakokinetika MeSH
- mebendazol analogy a deriváty krev chemie metabolismus farmakokinetika MeSH
- molekulární struktura MeSH
- ovce * MeSH
- stárnutí * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antinematodní látky MeSH
- flubendazole MeSH Prohlížeč
- mebendazol MeSH
Dicroceliosis, a lancet fluke infection, is a frequent parasitosis of small ruminants and the anthelmintic drug albendazole (ABZ) is effective in control of this parasitosis. The aim of our project was to study the metabolism of ABZ and ABZ sulphoxide (ABZ.SO) in lancet fluke. Both invitro (subcellular fractions of fluke homogenates) and exvivo experiments (adult flukes cultivated in medium) were performed for this purpose. ABZ was metabolised invitro by lancet fluke NADPH-dependent enzymes by two oxidative steps (sulphoxidation and sulphonation). The apparent kinetic parameters of these reactions have been determined. In the exvivo experiments, only ABZ sulphoxidation was observed. The stereospecificity in ABZ sulphoxidation invitro was slight, with preferential formation of (+)-ABZ.SO enantiomer. In contrast (-)-ABZ.SO formation predominated in exvivo experiments. Sulphoreduction of ABZ.SO occurred neither invivo nor exvivo. The detection of ABZ oxidative metabolites indicates the presence of drug metabolising oxidases in lancet fluke.
- MeSH
- albendazol analogy a deriváty farmakokinetika MeSH
- anthelmintika farmakokinetika MeSH
- biotransformace MeSH
- Dicrocoelium metabolismus MeSH
- dikrocelióza parazitologie veterinární MeSH
- nemoci jater parazitologie veterinární MeSH
- nemoci ovcí parazitologie MeSH
- ovce MeSH
- reprodukovatelnost výsledků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- albendazol MeSH
- albendazole sulfoxide MeSH Prohlížeč
- anthelmintika MeSH
Haemonchus contortus is one of the most pathogenic parasites of small ruminants (e.g., sheep and goat). The treatment of haemonchosis is complicated because of frequent resistance of H. contortus to common anthelmintics. The development of resistance can be facilitated by the action of drug metabolizing enzymes of parasites that can deactivate anthelmintics and thus protect parasites against the toxic effect of the drug. The aim of this project was to investigate the Phase I biotransformation of benzimidazole anthelmintic flubendazole in H. contortus and to determine the biotransformation of other model xenobiotics. For this purpose, in vitro (subcellular fractions of H. contortus homogenate) as well as ex vivo (live nematodes cultivated in flasks with medium) experiments were used. The results showed that cytosolic NADPH-dependent enzymes of H. contortus metabolize flubendazole via reduction of its carbonyl group. The apparent kinetic parameters of this reaction were determined (V'max=39.8+/-2.1 nM min(-1), K'm=1.5+/-0.3 microM). The reduction of flubendazole in H. contortus is stereospecific, the ratio of (-):(+) enantiomers of reduced flubendazole formed was 90:10. Reduced flubendazole was the only Phase I metabolite found. Effective reduction of other xenobiotics with carbonyl group (metyrapon, daunorubicin, and oracin) was also found. Significant activity of carbonyl-reducing enzymes may be important for H. contortus to survive the attacks of anthelmintics or other xenobiotics with carbonyl group.
- MeSH
- biotransformace MeSH
- Haemonchus účinky léků metabolismus MeSH
- hemonchóza veterinární MeSH
- mebendazol analogy a deriváty chemie farmakokinetika MeSH
- nemoci ovcí parazitologie MeSH
- ovce MeSH
- oxidoreduktasy metabolismus MeSH
- subcelulární frakce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- flubendazole MeSH Prohlížeč
- mebendazol MeSH
- oxidoreduktasy MeSH
Mycobacterium avium subsp. avium (MAA) of serotype 2 and genotype IS901+ and IS1245+ was cultured from 21 naturally infected hens (Gallus domesticus) from one smallholder aviary. From a total of 330 samples taken from hens, 124 mycobacteria were detected. Out of which MAA was detected in 103 (35.7%) of 288 tissues, in 4 (19.0%) of 21 swabs of cloacae and in 9 (42.9%) of 21 faeces samples, 8 other conditionally pathogenic mycobacterial species were also isolated. Tuberculous (TB) lesions were found in the liver, spleen and intestinal organs of seven hens. The isolates of MAA (n=58) from 16 infected hens (7 with TB lesions and 9 without TB lesions) were found to be of 3 IS901 RFLP types AE (n=48), AD (n=4) and E (n=6), where these MAA isolates are highly virulent to hens. Mixed infections with IS901 RFLP types (AE and AD) and (AE and E) were also evident in seven hens. From a total of 35 examined environmental samples, 23 mycobacterial isolates were detected. Out of which four (17.4%) MAA isolates of IS901 RFLP type AE and 19 (82.6%) other isolates of conditionally pathogenic mycobacteria were detected. The finding of identical IS901 RFLP types from both tissues and faecal isolates confirms that infected domestic hens are the principal source of infection for other susceptible hosts and lead to the contamination of the surrounding environment. The presence of different IS901 RFLP types in tissue isolates may indicate the repeated incidence of MAA infection and the occurrence of polyclonal infection.
- MeSH
- diagnóza MeSH
- feces mikrobiologie MeSH
- kloaka mikrobiologie MeSH
- kur domácí MeSH
- mikrobiologie životního prostředí * MeSH
- Mycobacterium avium klasifikace izolace a purifikace MeSH
- nemoci drůbeže mikrobiologie MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- ptačí tuberkulóza mikrobiologie patologie MeSH
- sérotypizace MeSH
- techniky typizace bakterií MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Basal activities of certain pheasant hepatic and intestinal biotransformation enzymes and modulation of their activities by anthelmintics flubendazole (FLBZ) and mebendazole (MBZ) were investigated in subcellular fractions that were prepared from liver and small intestine of control and FLBZ or MBZ treated birds. Several oxidation, reduction and conjugation enzyme activities were assessed. In the liver, treatment of pheasants by FLBZ or MBZ caused very slight or no changes in monooxygenase activities and conjugation enzymes. More significative changes were detected in small intestine. Metyrapone and daunorubicin reductase activities were increased by both substances in the liver. This is the first evidence that certain benzimidazoles modulate reductases of carbonyl group. With respect to the relatively slight extent of the changes caused by FLBZ or MBZ we can assume that repeated administration of therapeutic doses of both FLBZ and MBZ has probably no serious influence on pheasant biotransformation enzyme system.
- MeSH
- aktivace enzymů účinky léků MeSH
- anthelmintika farmakologie MeSH
- Galliformes metabolismus MeSH
- játra účinky léků enzymologie MeSH
- mebendazol analogy a deriváty farmakologie MeSH
- střeva účinky léků enzymologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- anthelmintika MeSH
- flubendazole MeSH Prohlížeč
- mebendazol MeSH
Parasitic infections can modify the host's ability to metabolize drugs and other xenobiotics by altering the biotransformation enzymes; these changes may have various pharmacological, toxicological or physiological consequences. In our study, several activities of liver biotransformation enzymes and in vitro metabolism of albendazole (ABZ) were tested and compared in non-infected mouflons (Ovis musimon) and in mouflons infected by lancet fluke (Dicrocoelium dendriticum). Subcellular fractions of liver homogenates were isolated from 5+5 mouflon rams (1-year-old) parasitologically negative or naturally infected by fluke. From the eight enzyme activities that were assayed, only two activities significantly differ in the case of Dicrocoelium-infected versus non-infected animals. In infected mouflons, a significant increase (53%) of thiobenzamide-S-oxidase (TBSO) activity, corresponding mainly to the activity of flavine monooxygenase (FMO), and significant decrease (60%) of glutathione-S-transferase (GST) activity was observed. In addition, dicrocoeliosis caused the enhancement of ABZ hepatic biotransformation. The velocity of the formation of (+)-ABZ sulfoxide and ABZ sulfone was significantly increased. However, the shifts in ABZ biotransformation were very mild that undesirable alterations in ABZ pharmacokinetic are not expected. From this point of view, the use of ABZ in the therapy of mouflon dicrocoeliosis in young animals can be recommended. The treatment of the same mouflons by other drugs that are mainly conjugated with glutathione, seems to be more problematic; hence, all consequences of documented reduced GST activity should be accounted.
- MeSH
- albendazol chemie farmakokinetika MeSH
- anthelmintika chemie farmakokinetika MeSH
- dikrocelióza metabolismus veterinární MeSH
- játra metabolismus MeSH
- molekulární struktura MeSH
- nemoci ovcí metabolismus MeSH
- ovce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- albendazol MeSH
- anthelmintika MeSH
Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.
- MeSH
- alkoholoxidoreduktasy metabolismus MeSH
- anthelmintika farmakologie MeSH
- fenbendazol farmakologie MeSH
- glukuronosyltransferasa metabolismus MeSH
- izoenzymy MeSH
- jaterní mikrozomy účinky léků enzymologie metabolismus MeSH
- mebendazol analogy a deriváty farmakologie MeSH
- nemoci prasat farmakoterapie enzymologie parazitologie MeSH
- parazitární nemoci střev farmakoterapie enzymologie veterinární MeSH
- prasata MeSH
- steroidhydroxylasy metabolismus MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- tenké střevo účinky léků enzymologie metabolismus MeSH
- western blotting veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkoholoxidoreduktasy MeSH
- anthelmintika MeSH
- fenbendazol MeSH
- flubendazole MeSH Prohlížeč
- glukuronosyltransferasa MeSH
- izoenzymy MeSH
- mebendazol MeSH
- steroidhydroxylasy MeSH
- systém (enzymů) cytochromů P-450 MeSH
