硒与维生素E对鸡马杜霉素急性中毒的保护作用

在实验条件下用7mg/kg bw.剂量的马杜霉不诱发鸡急性中毒，处理组鸡在给马杜霉素前给予硒（0.2mg/kg bw.剂量，内服）－维生素E（每kg饲料含200mg)7d，在给马杜霉素后给予硒（0.2mg/kg bw.剂量，内服）－维生素E（200mg/kg bw.剂量，肌注）4d，中毒组在给马杜霉素前后不给任何硒和维生素E，对照组既不给马杜霉素，也不给硒与维生素E。结果是：处理组鸡的死亡率显著低于中毒组（P＜0.05），且病鸡恢复比中毒组快。处理组的肝脏、心肌、骨骼肌的出血与变性比中毒组轻，但处理组与中毒组的肾脏的出血与变性的程度相似；处理组的血清GOT值、肝脏的脂质过氧化物的含量、肝脏过氧化氢酶的性均显著低于中毒组；但处理组的血清CK值与中毒组相比无显著性差异。结果表明硒与维生素E对鸡马杜霉素急性中毒有较好的保护作用。     

牛磺酸对马杜霉素中毒大鼠的保护作用

观察牛磺酸对大鼠马杜霉素中毒时的保护作用。将试验大鼠每天灌服马杜霉素进行染毒,且染毒前1 h腹腔注射牛磺酸保护,染毒5 d,继续注射牛磺酸2 d后处死,测定血清、肝脏、腿肌和心肌的丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、谷胱甘肽过氧化物酶（GSH-Px）活力和总抗氧化能力（T-AOC）。结果表明牛磺酸组的大鼠血清、肝脏、腿肌和心肌中SOD活性、GSH-Px活力、T-AOC均有所提高,MDA有所降低,与对照组、马杜霉素组比较,差异显著（P〈0.01,P〈0.05）。牛磺酸可以提高大鼠机体的抗氧化能力,对马杜霉素引起的脂质过氧化具有保护作用。     

鸡急性马杜拉霉素中毒的实验病理学研究

以28日龄鸡为试验动物，在饲料中添加不同剂量马杜拉霉素（0、5、6、7、8、9和10mg/kg)，对实验性马杜拉霉素中毒鸡的临床症状、剖检变化和组织病理学变化进行观察。结果马杜拉霉素急性中毒鸡表现腹泻、食欲下降、渴欲增加，翅膀下垂、腿无力或麻痹；剖检可见病鸡肝淤 血、轻度肿胀、呈微黄色；病理组织学变化为肝脂肪变性及心肌和腿肌出血。     

鸡白痢沙门氏菌感染雏鸡后体内的抗氧化酶活性及脂质过氧化物含变化

２日龄雏鸡人工感染鸡白痢沙门氏菌，于大量出现病变后剖杀，并分别测定心脏、肝脏、脾脏、肾脏、法氏囊中的超氧化物歧化酶（ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨＰｘ）、过氧化物酶（ＣＡＴ）的活性及脂质过氧化物（ＬＰＯ）的含量。结果表明：攻毒组与对照组相比，ＳＯＤ活性除心脏外，其余被测器官中均显著下降；ＧＡＳＨＰｘ和ＣＡＴ活性在各被测器官组织中均呈显著下降；而ＬＰＯ含量在含组织中均呈极显著地升高。     

低温应激对小鼠不同组织脂质过氧化状态的影响

为了研究低温应激对小鼠不同组织脂质过氧化状态的影响,试验选择健康清洁级昆明白小鼠40只,随机分为对照组和应激组,每组20只。采集对照组和经过-20℃处理120 min的低温应激组组织样品,测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果表明:与对照组相比,应激组小鼠肝脏、肾脏MDA含量显著升高(P<0.05),心肌、肺脏MDA含量有上升的趋势(P>0.05),腿肌MDA含量无明显变化(P>0.05);应激组小鼠肝脏、肾脏和肺脏SOD活性显著降低(P<0.05),心肌SOD活性有下降的趋势(P>0.05),腿肌SOD活性无明显变化(P>0.05)。说明冷应激对小鼠组织脂质过氧化反应的影响具有组织差异性特点,即对肝脏和肾脏影响最大,肺脏次之,心肌和腿肌最小。     

家禽营养对防御体系的影响

免疫系统是生物体对蛋白质异物的防御体系；肝脏微粒体细胞色素Ｐ－４５０依赖性药物代谢酶（ＭＣＰ－４５０）是生物体对脂溶性异物的防御体系。日粮中各种营养成分的含量对免疫系统和ＭＣＰ－４５０免疫体系都有不同程度的影响。     

雏鸡感染沙门氏杆菌后体内DAT活性和LPO含量的变化

二日龄雏鸡人工感染鸡白痢沙门氏杆菌，于大量出现病变时剖杀，并分别测定心脏、肝脏、脾脏、肾脏、法氏囊中过氧化氢酶（CAT）活性和脂质过氧化物（LPO）的含量。结果表明：攻毒组与对照组相比，各组织中CAT活性显著下降（P＜0.05），LPO值极显著地升高（P＜0.01）。     

日粮中添加天门冬氨酸镁对肉仔鸡肝脏和腿肌脂质过氧化状态的影响

研究日粮添加天门冬氨酸镁（MgAsp）对肉仔鸡肝脏和腿肌脂质过氧化状态的影响及其机理。将128只22日龄的AA肉仔鸡随机分配到对照组和加镁日粮组,每组8个重复,每个重复8只鸡,以玉米、豆粕为主要原料配制对照组日粮,在此基础上添加1％的MgAsp作为加镁组日粮。42日龄时,每个重复随机抽取1只鸡,颈静脉放血处死,收集血清、肝脏和腿肌等样品。试验结果表明,与对照组相比,加镁组肉仔鸡血清、腿肌和肝脏镁的含量分别提高了22％、21％和29％（P〈0．01）,加镁组肉仔鸡肝脏和腿肌中丙二醛（MDA）的含量分别降低了24%（P〈0．01）和29％（P〈0．01）,加镁组肉仔鸡肝脏中过氧化氢酶（CAT）和总超氧化物歧化酶（SOD）的活性分别提高了25％（P〈0．01）和14％（P〈0．05）,腿肌CAT的活性提高了37％（P〈0．01）,日粮添加MgAsp显著降低腿肌中活性氧（ROS）的含量（P〈0．01）。两组肉仔鸡腿肌和肝脏中不饱和脂肪酸的总含量差异不显著（P〉0．05）。上述结果说明,玉米-豆粕日粮中添加MgAsp可以有效降低肝脏和腿肌中MDA的产量;腿肌中CAT活性的提高和ROS产量的降低是日粮添加MgAsp降低腿肌中脂质过氧化水平的原因;肝脏中CAT和SOD活性的提高是日粮添加MgAsp降低肝脏中脂质过氧化水平的原因。     

马杜霉素在鸡组织中残留消除及临床毒性的研究

本文报道以3.0、5.0、7.0和9.0mg/kg马杜霉素剂量水平添加到饲料中饲喂AA肉鸡,研究马杜霉素对肉鸡的毒性作用及其在鸡组织中的残留消除。从临床症状、增重与饲料转化、死亡率、血清生化参数以及组织病理学等方面研究结果表明,饲料中添加3.0－5.0mg/kg剂量马杜霉素对肉鸡是安全的,未见任何毒副作用,而7.0-9.0mg/kg剂量则引起肉鸡中毒,中毒表现为,增重和饲料转化率明显下降,血清AST异常升高,心脏和肝脏出现病理变化。残留消除研究表明,马杜霉素主要残留于肉鸡的脂肪和肝脏,其次是肾脏,肌肉中残留最少。马杜霉素以5.0mg/kg剂量添加于饲料中饲喂肉鸡,停药2－3d,肉鸡组织中马杜霉素的残留量低于最高残留限量的规定。.     

雏鸵鸟马杜霉素中毒实例与试验

湖南某鸵鸟场用“加福”治疗雏鸵鸟球虫病时 ,由于用药不当而使 2只雏鸟中毒死亡。为进一步摸清鸵鸟马杜霉素中毒的剂量、经过及发病出现的特征性症状 ,作为兽医临床诊断的依据 ,进行马杜霉素中毒试验。结果显示 ,实验与临床病例表现的主要症状基本一致 ,拉稀粪、痉挛、口腔内有大量带血丝的粘液 ,剖检发现皮下、心外膜、腺胃、肌胃浆膜层和肌层出血 ,小肠粘膜层充血出血。雏鸵鸟马杜霉素中毒从摄取毒物到死亡时间为 8～ 10h ,呈现亚急性中毒症状。     

A lipopolysaccharide-induced acute phase response in the pig is associated with a decrease in hepatic cytochrome P450-mediated drug metabolism

Drug disposition, including hepatic drug metabolism, is markedly affected by infection, inflammation and other conditions that invoke the acute phase response. In the present study, an Escherichia coli lipopolysaccharide (LPS)-induced acute phase response model was developed in pigs. This model was used to study the effects of the acute phase response on drug disposition and hepatic drug metabolism in vivo and in microsomal preparations. The results obtained were compared with those from Actinobacillus pleuropneumoniae -infected pigs. Intermittent intravenous administration of LPS induced a mild acute phase response as evidenced by increased rectal body temperatures, anorexia and increased cytokine (TNF-α and IL-6) serum levels within 1-2 h after the first LPS injection. The acute phase response is associated with a pronounced decrease of antipyrine plasma clearance (control 8.5 ± 0.8 vs. LPS 2.2 ± 0.7 mL/min.kg). Furthermore, total cytochrome P450 content and microsomal cytochrome P450-dependent activities were significantly decreased after 24 h. The decrease in cytochrome P450 activities was accompanied by losses of cytochrome P4501A and P4503A apoproteins. The microsomal glucuronidation rate of 1-naphthol was not affected in LPS-treated pigs. Comparing the LPS model with our previous findings in the Actinobacillus pleuropneumoniae model showed a remarkable similarity with regard to the effects on hepatic drug metabolism.     

The effect of monensin, tiamulin and the simultaneous administration of both substances on the microsomal mixed function oxidases and on the peroxide formation in broilers

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.     

Hepatic and pulmonary enzyme activities in horses

OBJECTIVE: To determine hepatic and pulmonary phase-I and phase-II enzyme activities in horses. SAMPLE POPULATION: Pulmonary and hepatic tissues from 22 horses that were 4 months to 32 years old. PROCEDURE: Pulmonary and hepatic tissues from horses were used to prepare cytosolic (glutathione S-transferase and soluble epoxide hydrolase) and microsomal (cytochrome P450 monooxygenases) enzymes. Rates of microsomal metabolism of ethoxyresorufin, pentoxyresorufin, and naphthalene were determined by high-performance liquid chromatography. Activities of glutathione S-transferase and soluble epoxide hydrolase were determined spectrophotometrically. Cytochrome P450 content was determined by carbon monoxide bound-difference spectrum of dithionite-reduced microsomes. Activity was expressed relative to total protein concentration. RESULTS: Microsomal protein and cytochromeP450 contents were detectable in all horses and did not vary with age. Hepatic ethoxyresorufin metabolism was detected in all horses; by comparison, pulmonary metabolism of ethoxyresorufin and hepatic and pulmonary metabolism of pentoxyresorufin were detected at lower rates. Rate of hepatic naphthalene metabolism remained constant with increasing age, whereas rate of pulmonary naphthalene metabolism was significantly lower in weanlings (ie, horses 4 to 6 months old), compared with adult horses. Hepatic glutathione S-transferase activity (cytosol) increased with age; however, these changes were not significant. Pulmonary glutathione S-transferase activity (cytosol) was significantly lower in weanlings than adult horses. Hepatic and pulmonary soluble epoxide hydrolase did not vary with age of horses. CONCLUSIONS AND CLINICAL RELEVANCE: Activity of cytochrome P450 isoforms that metabolize naphthalene and glutathione S-transferases in lungs are significantly lower in weanlings than adult horses, which suggests reduced ability of young horses to metabolize xenobiotics by this organ.     

Comparison of the effects of Sesbania drummondii on the hepatic microsomal monooxygenase systems of chickens and rats

Sesbania drummondii, a toxic leguminous shrub found throughout the southeastern United States, induces different responses in chicken vs rat hepatic microsomal monooxygenase systems. Groups of 4- to 8-week-old Sprague-Dawley rats and White Leghorn chickens were given extracts of S drummondii by gavage for 3 days. Doses, which were 0.4 and 0.8% of daily body weights, respectively, for the rats and chickens, were adjusted to induce similar clinical lesions in the 2 species. The hepatic microsomal monooxygenase systems of control and treated animals were compared, using cytochrome P-450 content, cytochrome b5 content, NADH- and NADPH-cytochrome c-reductase activity, and 6 cytochrome P-450 mediated enzyme activities. Increases of twofold in the cytochrome P-450 content, NADPH-cytochrome c-reductase, aminopyrine-N-demethylase, aniline hydroxylase, ethoxycoumarin-O-deethylase, and aryl hydrocarbon hydroxylase activities; fourfold in the aldrin epoxidase activity; and 15-fold in the ethoxyresorufin-O-deethylase activity were observed in the S drummondii-treated chickens. In contrast, the treated rats had nearly twofold decreases in these values, suggesting a species-specific effect of S drummondii on microsomal monooxygenase systems, ie, induced with S drummondii.     

Toxicity of dietary monensin in quail

Quail were fed monensin to determine liver damage, as measured by changes in activities of serum enzymes and liver microsomal enzymes. Monensin fed at a therapeutic level of 110 ppm for 2 weeks produced an increase in cytochrome P-450 and cytochrome b5 and induction of the activities of benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, with no changes in the activities of serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). On the other hand, quail fed 110 ppm, 220 ppm, and 330 ppm monensin in feed for 6 weeks showed a significant rise in SDH and AST activities at 330 ppm but not at 110 ppm and 220 ppm. The manifestations of liver toxicity observed at 330 ppm were accompanied by a significant decrease in all the aforementioned hepatic microsomal mixed-function oxidases. In contrast, quail fed monensin at 110 ppm and 220 ppm for 6 weeks produced no change in these parameters except for benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, which were significantly increased in birds fed 220 ppm of monensin.     

Effect of acute salinomycin-tiamulin toxicity on the lipid peroxide and antioxidant status of broiler chicken.

The combined effect, if any, of salinomycin poisoning and salinomycin-tiamulin interaction on lipid-peroxidative processes and the antioxidative defence system of the liver was studied in domestic fowl. Male broilers (28-day-old), reared on a diet containing 60 mg/kg salinomycin, were treated intraoesophageally with salinomycin (140 mg/kg body mass) or tiamulin (50 mg/kg body mass). Malondialdehyde, reduced glutathione and cytochrome P-450 concentrations as well as glutathione peroxidase and catalase activities of the liver were determined. Liver malondialdehyde concentration rose in the salinomycin-treated group while the amount of cytochrome P-450 increased in both groups treated. Glutathione concentration and glutathione peroxidase activity of the liver decreased rapidly but hepatic catalase activity increased in both groups after the treatment. Manifestation of the effect exerted by salinomycin and salinomycin-tiamulin on lipid-peroxidative processes nearly coincided with the onset of clinical signs and preceded the increase of hepatic cytochrome P-450 concentration. According to the results, the background of the previously reported incompatibility between salinomycin and tiamulin is the synergistic effect exerted on the antioxidant (glutathione) system.     

Effect of Gossypol on Hepatic and Serum γ-glutamyltransferase Activity in Rats

A single intraperitoneal dose (25 mg/kg) of gossypol given to male Sprague-Dawley rats caused marked changes in the activity of the hepatic and serum -glutamyltransferase (GGT) and microsomal monooxygenases. The GGT activity in liver homogenate, S-9 supernatant fraction and microsomes was significantly depressed; however, the level of serum GGT was elevated. While the hepatic glutathione concentration was not greatly changed, the aminopyrine N-demethylase activity and microsomal cytochrome P450 content of the liver were significantly decreased in the treated rats. At necropsy, the livers of the treated rats appeared generally pale with distinct pinpoint foci. Histopathological examination of the liver showed degenerative changes and coagulative necrosis. The results indicate that gossypol is a strong hepatotoxic agent which can produce severe hepatic damage.     

日粮镁对肉仔鸡腿肌中活性氧产量的影响

本试验目的是研究日粮镁水平对肉仔鸡腿肌中活性氧(reactive oxygen species , ROS)产量的影响。96只AA肉仔鸡随机分配到低镁日粮组和对照组,每组6个重复,每个重复8只鸡,分别喂以镁含量1 .2 g/kg或2 .4 g/kg的日粮。与对照组相比,低镁组肉仔鸡腿肌中谷胱甘肽(glutathione , GSH)的含量降低了27 %(P<0 .01) ,丙二醛(malondialdehyde, MDA)的含量提高了40 %(P<0 .01)。采食低镁日粮的肉仔鸡腿肌匀浆液的ROS信号峰的高度显著高于对照组(P<0 .01)。对照组腿肌镁的浓度(30 .27 mg/kg)显著高于低镁组腿肌镁的浓度(27 .40 mg/kg)。腿肌中铁、钙的含量在两组之间差异不显著(P>0 .05)。与对照组相比,低镁组腿肌线粒体复合酶Ⅰ、Ⅱ、Ⅲ、Ⅳ的活性分别提高了28 %、23 %(P<0 .01)、35 %(P<0 .01)和30 %,线粒体复合酶Ⅰ、Ⅱ、Ⅲ、Ⅳ的活性与ROS产量之间呈显著的负相关关系(P<0 .05)。除C18∶2的含量显著高于对照组外,其他多不饱和脂肪酸含量在两组之间没有差异。本试验结果表明低镁日粮实质性地提高肉仔鸡腿肌中ROS的产量,低镁日粮降低腿肌中镁的浓度,诱导了线粒体呼吸链酶活性升高,从而提高了ROS的产量。     

Tiamulin selectively inhibits oxidative hepatic steroid and drug metabolism in vitro in the pig

The simultaneous use of the antibiotic tiamulin with certain ionophoric antibiotics (monensin, salinomycin) may give rise to a toxic interaction in pigs and poultry. In the present study, effects of tiamulin on hepatic cytochrome P450 activities in vitro were studied using pig liver microsomes. When tiamulin was added to the incubation medium the N-demethylation rate of ethylmorphine and the hydroxylation of testosterone at the 6β- and 1 lα- positions was sirongly inhibited. Tiamulin inhibited these activities more than SKF525A or cimetidine, but less than ketoconazole. The microsomal N-demethylation rate of erythromycin and the hydroxylation of testosterone at the 28- position were inhibited to a lesser degree, whereas the ethoxyresorufin-O-deethylation, aniline hydroxylation and testosterone hydroxylations at the 15α- and 15β- positions were not affected by tiamulin. No in vitro complexation by tiamulin of cytochrome P450 resulting in a loss of CO-binding capacity could be demonstrated. Results from the present study suggest a selective inhibition of cytochrome P450 enzymes in pigs, probably belonging to the P4503A subfamily. The mechanism of this interaction is still unclear. However, interactions between tiamulin and those veterinary drugs or endogenous compounds which undergo oxidative metabolism by P450 enzymes must be considered. More research is needed to reveal which of the P450 enzymes are affected by tiamulin in order to improve the understanding and probably the predictability of this interaction.