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1.
The effect of phenobarbitone against signal grass (Brachiaria decumbens) toxicity was studied in 26 male crossbred sheep. Grazing on signal grass significantly decreased the concentration of cytochrome P-450 and the activity of drug metabolizing enzymes, viz. aminopyrine-N-demethylase, aniline-4-hydroxylase, UDP- glucuronyltransferase and glutathione-S-transferase in liver and kidneys of affected sheep.Oral administration of phenobarbitone (30 mg/kg body weight) for five consecutive days before grazing on B. decumbens pasture, and thereafter, for three consecutive days every two weeks, resulted in significant increases in hepatic and renal activities of drug-metabolizing enzymes. The induction of drug metabolizing activity in sheep grazing on signal grass group was found to be lower than in animals given phenobarbitone alone. Induction by phenobarbitone provided a degree of protection against the toxic effects of B. decumbens as indicated by the delay in the appearance of signs of toxicity. Furthermore, these were much milder compared to those in the sheep not treated with phenobarbitone. The present study suggests that phenobarbitone-type cytochrome P-450 isoenzyme-induction may increase resistance against signal grass (B. decumbens) toxicity in sheep.  相似文献   

2.
Brachiaria decumbens is an extremely productive tropical grass due to its aggressive growth habit and its adaptation to a varied range of soil types and environments. As a result of the vast availability, treated B. decumbens demonstrates as a promising local material that could be utilised as an improved diet for sheep and goats. Despite the fact that the grass significantly increases weight gains in grazing farm animals, there were many reports of general ill-thrift and sporadic outbreaks of photosensitivity in livestock due to the toxic compound of steroidal saponin found in B. decumbens. Ensiling and haymaking were found to be effective in removing toxin and undesirable compounds in the grass. Biological treatments using urea, activated charcoal, polyethylene glycol, and effective microorganisms were found to be useful in anti-nutritional factor deactivation and improving the nutritive values of feedstuffs. Besides, oral administration of phenobarbitone showed some degree of protection in sheep that fed on B. decumbens pasture. In this review, we aim to determine the effect of B. decumbens toxicity and possible treatment methods on the grass to be used as an improved diet for small ruminant.  相似文献   

3.
Brachiaria spp. are the most important grasses for ruminants in central-western Brazil. However, the use of these pastures is limited by their toxicity due to steroidal saponins. This experiment was conducted for 60 days to demonstrate the resistance of sheep raised on Brachiaria spp. pastures to steroidal saponin poisoning. The experiment was composed by 48 animals randomly divided into four groups (n?=?12). Among them, 32 4- to 5-month-old castrated male crossbred Santa Inês sheep, originating from flocks that had been grazing on Brachiaria spp. for more than three consecutive years, and 16 were non-adapted (naïve) sheep from flocks that never had prior contact with pastures of Brachiaria spp. were randomly divided into four groups. Each of the four experimental groups was composed by eight adapted and four non-adapted animals. The four experimental groups were introduced into paddocks, each of which contained a single grass: either Brachiaria decumbens, Brachiaria brizantha, Panicum maximum, or Andropogon gayanus. The addition of the naïve sheep to the groups was designed to detect pastures’ toxicity to naïve sheep and to adjust the stocking rate to optimize the use of forage. The weight gains of sheep grazing on B. decumbens, B. brizantha, and P. maximum were similar; however, the A. gayanus group showed lower weight gains compared with the other groups (P?<?0.05). The mean serum activities of γ-glutamyltransferase in the sheep grazing on B. decumbens were higher than those in the sheep from the other groups. No significant differences among the groups were found in aspartate aminotransferase, creatinine, albumin, or total protein serum concentrations. No clinical signs were observed in the adapted sheep in any of the pastures. Of the four non-adapted sheep introduced into the B. decumbens pasture, two showed clinical signs of steroidal saponin poisoning, and one died. No clinical signs were observed in the non-adapted sheep in the other pastures. The saponin (protodioscin) concentrations in the pastures varied from 3.3 to 12.2 g/kg DM in B. decumbens, from 2.8 to 9.1 g/kg DM in B. brizantha, and from 1 to 1.5 g/kg DM in A. gayanus. No saponins were found in P. maximum. It is concluded that sheep from flocks reared in pastures of B. decumbens and B. brizantha were resistant to steroidal saponin poisoning and showed similar weight gains to those of sheep grazing in other tropical pastures.  相似文献   

4.
Although Brachiaria decumbens was not toxic when fed to cattle, the infusion of rumen liquor from B. decumbens intoxicated sheep into the rumen of cattle produced evidence suggesting hepatic and renal dysfunction. Several biochemical changes were observed including increases in serum aspartate amino transferase, serum creatinine and blood urea nitrogen and a marked reduction in the plasma bromosulphthalein clearance.  相似文献   

5.
Contents The activities of cytochrome P-450 and the P-450 dependent aminopyrine -N-demethylase and aniline 4-hydroxylase (Phase I, drugmetabolizing enzymes) and UDP-glucurony-l-transferase (a Phase II drug-metabolizing enzyme) have been measured in vitro in the placenta and liver of camels and sheep during pregnancy. The placenta of late pregnancy of both species produced 50% of the activity in maternal liver of phase I drug-metabolizing enzymes. The rate of O-aminophenol glucuronide was low both in placenta and foetal liver. It is suggested that close to term the placenta and foetal liver are capable of metabolizing drugs by P-450 mediated phase I reactions. Inhalt: Arzneimittel-metabolisierende Enzyme von Plazenta und Fötus bei Kamel und Schaf Während der Trächtigkeit wurde die Aktivität der Cytochrom P-450 abhängigen Aminophyrine -N-Demethylase, Anilin 4-Hydroxylase (Phase I metabolisierendes Enzym) und der UDP-Glucuronyl-1 Transferase (Phase II metabolisierendes Enzym) unter in vitro Bedingungen in Plazenta- und Lebergewebe von Kamelen und Schafen gemessen. In beiden Tierarten produzierte die Plazenta während der späten Trächtigkeit 50% der Aktivität, wie sie die mütterliche Plazenta der “Phase I—Enzyme” produziert. Die O-Aminophenol Glucuronide waren dagegen gering in Plazenta und fetaler Leber. Es wird angenommen, daβ die Plazenta und die fetale Leber kurz vor der Geburt in der Lage sind, Arzneimittel durch die Cytochrom P-450 abhängige Phase I-Reaktionen zu metabolisieren.  相似文献   

6.
Maturational development of drug-metabolizing enzymes in sheep   总被引：1，自引：0，他引：1  
A qualitative and quantitative assessment was made of the development of hepatic drug-metabolizing enzymes (DME) in sheep as part of a study of the ability of the food-producing species to metabolize drugs. The following DME and components were measured in this study: cytochromes P-450 and b5 and NADPH and NADPH-dependent reductases associated with each of these cytochromes; cytochrome P-450-mediated reactions, including aniline and coumarin hydroxylases, aminopyrine N-demethylase, and 7-ethoxycoumarin 0-deethylase; a uridine diphosphoglucuronic acid glucuronyl transferase with 4-methylumbelliferone as substrate; and glutathione-S-transferase with dinitrochlorobenzene and dichloronitrobenzene as substrates. Amounts or activities of most of these components and enzymes increased up to and beyond the time of weaning. Amount of cytochrome b5 and uridine diphosphoglucuronic acid transferase activity were not affected by age, whereas NADPH cytochrome c (P-450) reductase activity actually decreased after weaning. In some instances (eg, coumarin hydroxylase, cytochrome P-450, and dinitrochlorobenzene-glutathione-S-transferase), differences from preweaning DME values were observed only after sheep were greater than or equal to 6 months old. All other DME activities were definitely increased, compared with the values in lambs before weaning (0 to 12 weeks old). Approximately a third of the sheep studied had some type of clinical disease that might have affected the DME activities. Diseases were classified as sore mouth, pneumonia, foot rot, parasitism, and systemic bacterial infections. Except in a few instances, these diseases had minimal effect on DME activities measured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
An examination was made of the relationship in Romney sheep between selenium deficiency and (i) the state of the liver drug metabolising enzyme system, (ii) subclinical liver damage, (iii) susceptibility to facial eczema, and (iv) susceptibility to ryegrasss staggers. The microsomal electron transport detoxifying enzymes based on cytochrome P-450 were unaffected by Se deficiency, suggesting that these enzymes are uninduced on ryegrass/clover pastures. Selenium deficiency had no effect on sporidesmin-induced liver damage, which makes it unlikely that peroxidative events countered by Se-dependent glutathione peroxidase (E.C.1.11.10) have a major role in the mechanism of sporidesmin toxicity. Selenium deficiency did appear to suppress the development of photosensitisation. There was no major effect on ryegrass staggers and no deficiency-induced subclinical liver damage.  相似文献   

8.
The conjugated linoleic acid (CLA) content of grazing sheep and goat milk fat, throughout their lactation period, was examined. Six sheep and six goat representative farms were selected at random and milk samples were taken at monthly intervals for fatty acids profile determination. Sheep and goat nutrition was based on natural grazing and on supplementary feeding during the winter months. From April onwards, grazing native pastures was the only source of feed for sheep and goats. The University farm whose sheep are kept indoors all year round without any grazing, was also used as reference. Fifteen individual milk samples were also taken in April from a sheep and goat farm respectively, in order to see the variability of CLA inside the farm. The results showed that: a. the CLA content of grazing sheep and goat milk fat increased significantly in April–May (early growth stage of grass) and then declined while that of indoors kept sheep was more or less constant during the same period, b. the isomers cis-9, trans-11 and trans-10, cis-12 of CLA were found in grazing sheep milk fat, while in indoors kept sheep and goats' milk fat only the cis-9, trans-11 isomer was found, c. the CLA content of sheep milk fat was much higher than that of goats, d. a negative correlation between sheep milk fat and CLA content was found and e. there was considerable variation in milk fat CLA content between sheep and goat farms and inside the farms.  相似文献   

9.
Microsomal arylhydrocarbon (benzo[a]pyrene) hydroxylase activity in hyperplastic nodules in the livers of rats was decreased by feeding 2-acetylaminofluorene in their diet to 10% of that without 2-acetylaminofluorene feeding. By immunoblotting analysis with the antibodies raised against P-450/B[a]P, which is a form of cytochrome P-450 catalyzing benzo[a]pyrene hydroxylation in liver microsomes of untreated rats, it was shown that P-450/B[a]P content was decreased in the microsomes prepared from the nodular tissues. Microsomal UDP-glucuronyltransferase activity toward phenolic xenobiotics such as 1-naphthol and 4-nitrophenol was increased by 4.5-5.0-fold in the nodular tissues. This increase was inhibited by the addition of antibodies raised against GT-1, a form of UDP-glucuronyltransferase glucuronizing phenolic xenobiotics. Immunoblotting analysis with the antibodies against GT-1 showed that a protein band corresponding to GT-1 was increased in the microsomes from nodular tissues. The increased UDP-glucuronyltransferase also had about 4,000 daltons "high mannose" oligosaccharide(s) like GT-1. The decreases of P-450/B[a]P and increases of GT-1 were observed mainly in nodular foci of the liver tissues. These results indicate that in liver nodules, decreased cytochrome P-450-dependent benzo[a]pyrene hydroxylase activity and increased UDP-glucuronyltransferase activity toward phenolic xenobiotics result from the decrease of the P-450 corresponding to P-450/B[a]P and the increase of the GT corresponding to GT-1.  相似文献   

10.
Vinblastine is a vinca alkaloid used either as a single agent or in combination therapy for the treatment of canine mast cell tumours and lymphomas. The objective of this study was to determine which isoform of cytochrome P450 enzyme is responsible for the majority of vinblastine metabolism in dogs. A panel of eight recombinant canine cytochrome P450 enzymes (CYP1A1, CYP1A2, CYP3A12, CYP3A26, CYP2B11, CYP2C41, CYP2C21 and CYP2D15) were incubated in vitro with vinblastine. Findings were confirmed by the use of canine polyclonal antibodies of cytochrome P450 enzymes (CYP1A1, CYP3A12, CYP2B11 and CYP2C21) that were pre‐incubated with individual and pooled hepatic microsomes that were purified from canine liver. Substrate depletion was observed in the presence of recombinant CYP3A12, whereas depletion did not substantially occur when microsomes were pre‐incubated with polyclonal antibodies against CYP3A12. These findings confirmed that CYP3A12 is the major cytochrome P450 isoform responsible for the metabolism of vinblastine in dogs.  相似文献   

11.
Imepitoin is a novel anti‐epileptic licensed in the European Union for the treatment of canine idiopathic epilepsy. The aim of this study was to characterize the pharmacokinetics of imepitoin in dogs and to evaluate the interaction with drug metabolizing enzymes. Upon administration of imepitoin tablets at a dose of 30 mg/kg to beagle dogs, high plasma levels were observed within 30 min following oral dosing, with maximal plasma concentrations of 14.9–17.2 μg/mL reached after 2–3 h. In a crossover study, co‐administration of imepitoin tablets with food reduced the total AUC by 30%, but it did not result in significant changes in Tmax and Cmax, indicating lack of clinical relevance. No clinically relevant effects of sex and no accumulation or metabolic tolerance were observed upon twice daily dosing. Following single dose administration of 10–100 mg/kg, dose linearity was found. Administering [14C] imepitoin, high enteral absorption of 92% and primary fecal excretion were identified. Plasma protein binding was only 55%. At therapeutic plasma concentrations, imepitoin did not inhibit microsomal cytochrome P450 family liver enzymes in vitro. In rats, no relevant induction of liver enzymes was found. Therefore, protein binding or metabolism‐derived drug–drug interactions are unlikely. Based on these data, imepitoin can be dosed twice daily, but the timing of tablet administration in relation to feeding should be kept consistent.  相似文献   

12.
Microsomal and cytosolic enzymes that metabolize xenobiotics were measured in composite samples representing entire livers and in samples from three lobes, using livers of cattle, goats and sheep. Within individual species, concentrations of cytochrome P-450 and b5 and activities of NADPH cytochrome c reductase, aldrin epoxidase, aminopyrine N-demethylase, ethoxycoumarin O-deethylase, microsomal and cytosolic stilbene oxide (epoxide) hydrolase and glutathione S-transferase were not different (P greater than .05) among the various hepatic lobes. Among species, several activities differed (P less than .05), with cattle livers generally having lower values than sheep or goats.  相似文献   

13.
Microsomal and cytosolic preparations of hepatic, renal, ileal and ruminal tissues of cattle and sheep were used to measure oxidative, hydrolative and conjugative biotransformations of 11 xenobiotic substrates. Within species, enzyme activities were generally higher (P less than .05) in hepatic than non-hepatic tissue but, in both species, non-hepatic tissue exhibited considerable capacities for metabolizing certain substrates. Sheep rumen wall (with papillae) was notably high in cytochrome P-450 content (34% of hepatic value), in glutathione conjugation of ethacrynic acid (223% of hepatic activity; P less than .05), and UDP-glucuronidation of estrone (290% of hepatic activity; P less than .05). Sheep differed (P less than .05) from cattle, having lower cytochrome P-450 content in liver and ileum (but not kidney); lower N-demethylase activity in liver, but two- to threefold higher activity in kidney; lower sulfotransferase activity in liver and kidney; and higher glutathione S-transferase activity toward certain substrates. UDP-glucuronidation varied too widely among substrates to afford strong generalization in comparisons among tissues or between species. Non-hepatic tissues in ruminants exhibit considerable capacities for oxidative, hydrolative and conjugative metabolism of xenobiotics. Sheep and cattle differ widely in hepatic and non-hepatic capacities for biotransforming certain xenobiotics.  相似文献   

14.
SUMMARY Cashmere goats and Merino sheep were grazed together at 7.5 animals per ha on annual rye grass and clover pasture in southern Victoria, a winter rainfall area. Intake of parasitic larvae was measured in oesophageal extrusa samples collected from 2 animals of each species, 4 times in one week, on 7 occasions between mid-March (autumn) and mid-June (winter). Pasture contamination with larvae was measured at the same times. The number of larvae per kg of green grass was lower than on green clover; the most heavily contaminated portion of the pasture was the mat of dead herbage on the ground. The diet selected by goats contained more green grass and dead herbage and less clover that that of sheep (P < 0.01). Goats ingested 643 infective trichostrongylid larvae per kg dry matter intake (DMI) versus 274 per kg DMI for sheep in autumn, increasing to 1892 versus 1143 in early winter. The heavier trichostrongylid burdens of goats compared with sheep, when grazed together, are due in part to greater rates of infection consequent on different grazing patterns as well as greater susceptibility to infection.  相似文献   

15.
本试验旨在研究不同物候期天然牧草中所含的营养成分对放牧绵羊瘤胃内环境的影响。分别在牧草生长的不同时期（绿草期、盛草期和枯草期）选择不同的样方测定其混合牧草的营养成分,同时段选择6只放牧绵羊测定其瘤胃pH,氨态氮（NH3-N）及挥发性脂肪酸（VFA）含量。结果显示：①牧草中粗蛋白质（CP）含量在绿草期含量最高（13.95%）,显著高于其他阶段（P < 0.05）,而枯草期最低,为5.14%;中性洗涤纤维（NDF）随着牧草的生长不断增加,酸性洗涤纤维（ADF）在绿草期含量最少。②瘤胃内环境参数随着不同物候期牧草中营养成分的变化而变化,瘤胃pH在盛草期显著低于其他阶段（P < 0.05）,NH3-N含量在枯草期显著低于其他两个阶段（P < 0.05）,VFA含量在枯草期最低,盛草期显著高于绿草期（P < 0.05）。综上所述,放牧绵羊在枯草期由于摄入的CP含量减少,NDF增加,导致消化率降低,不能满足放牧绵羊的营养需要,故在枯草期到绿草期这一阶段应对其进行合理补饲,调控瘤胃发酵,以改善瘤胃内环境,提高其对营养物质的吸收。  相似文献   

16.
The influence of Monensin, Tiamulin and the simultaneous administration of the two substances on the microsomal, mixed function oxidases was studied on cockerels. Monensin was seen to cause a slight depression in the amount of cytochrome P-450 and cytochrome b5 as well as in the activities of aniline-p-hydroxylase, p-nitrophenol-hydroxylase and p-nitroanisole-O-demethylase. Tiamulin induced a moderate increase in the amount of cytochrome P-450 and in the activities of aniline-p-hydroxylase, p-nitrophenol-hydroxylase and aminopyrine-N-demethylase. The combined administration of monensin and tiamulin resulted in marked induction of the microsomal enzymes; the amount of cytochrome P-450 reduced by metyrapone or carbon monoxide increased 2.5 or 2-times, respectively, and the activities of the tested microsomal hydroxylases and demethylases showed also an expressed increase. At the same time the formation of lipid peroxides also markedly increased and the GSH concentration was reduced. In conclusion, the results of the investigations indicate that the simultaneous application of monensin and tiamulin cause a marked induction of the drug-metabolizing microsomal enzymes and a significant increase in the lipid peroxide formation.  相似文献   

17.
The administration of xenobiotics such as phenobarbital (PB) and chlorinated hydrocarbons to rats, mice and several other species has been shown to increase the level of hepatic mixed function oxidases. Experiments were conducted to establish the effect of dose of PB, sex of animals, and effect of interval from dose to measurement on concentration of hepatic enzymes in barrows and gilts 6 to 9 mo of age and weighing 100 to 120 kg. Animals given 1 or 2 g PB for 3 d had higher concentrations of microsomal protein cytochrome b5 and P-450 and NADPH cytochrome c reductase than control animals (P less than .01). Animals given 2 g PB had 3.5 times as much cytochrome P 450 as did controls. Barrows and gilts did not differ from each other in any variables measured (P less than .20). In a study of the time course of induction all animals given PB had higher levels of microsomal protein, cytochrome P-450 and reductase in 24 h than controls; however, cytochrome b5 was depressed on d 1 and was elevated by d 3. Concentration of cytochrome P-450 reached a maximum by d 7 (P less than .01); cytochromes b5 and c reductase reached a maximum by d 9 and 3, respectively (P less than .01). Levels of cytochrome P-450 were higher in gilts than in barrows on all days following PB treatment (P less than .04). Microsomal protein, cytochrome b5, cytochrome P-450 and reductase remained elevated for 6 d after the last treatment with PB.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

18.
To compare the effect of fenbendazole on the liver and liver microsomal mono-oxygenases of goats, quail and rats, an oral dose of 25 mg/kg was administered to the animals daily for 9 consecutive days. On the tenth day, blood samples and livers were collected from both the control and the treated animals for preparation of serum and microsomes respectively. Determination of the activities of sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum samples showed that there was no significant increase in the activities of these enzymes in the treated animals as compared to their corresponding controls, suggesting no liver damage. Similarly, no significant difference in the amount of microsomal cytochrome P-450 was found between the control and the treated animals of the same species. Compared to their respective controls, the activities of microsomal benzphetamine N-demethylase and aniline hydroxylase were almost unchanged in the treated goats and rats. However, fenbendazole treatment appeared to enhance the activity of these two microsomal enzymes in quail. The results indicate that fenbendazole is not liver toxic to goats, quail or rats at a dose rate of 25 mg/kg.  相似文献   

19.
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20.
The nutritive value of four subtropical grasses (Panicum maximum, Anthephora pubescens, Digitaria eriantha and Chloris gayana) standing hay were compared in terms of qualitative intake and partial digestibility by sheep. The species differed significantly in terms of diet quality selected by sheep grazing the standing hay. The rumen ammonia nitrogen (NH3-N), total volatile fatty acid and propionic acid concentrations of sheep grazing P. maximum and A. pubescens were higher than those sheep grazing D. eriantha and C. gayana standing hay. Organic matter intake (OMI) (g kg?1 W0.75 d?1), nitrogen intake (g d?1), digesta flow, the total N flow, NH3-N flow, non-ammonia nitrogen (NAN) flow and NAN disappearance (g d?1) in the ileum were higher for sheep grazing P. maximum than for those grazing the other standing hays. The organic matter disappearance in the stomach and small intestine of sheep grazing P. maximum and D. eriantha standing hay was higher than for those sheep grazing either A. pubescens or C. gayana standing hay. The NAN flow/N intake were the highest for sheep grazing P. maximum and A. pubescens compared to C. gayana. The NAN digestibility was, however, not significantly different among the four species. The standing hays (except for C. gayana) seemed to have the capacity to meet the N requirement of the sheep for production, but the OMI (g kg?1 W0.75 d?1) was not sufficient to support maintenance requirement of the sheep.  相似文献   

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