牛磺酸拮抗马杜霉素毒性作用的研究
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摘要
当前以马杜霉素为代表的离子载体类抗球虫药在我国广泛使用,临床上畜禽中毒时常发生。由于聚醚类抗生素中毒时其确诊比较困难,故一旦发生中毒常造成重大的经济损失。目前,对于离子载体抗生素的中毒无特效解毒药。本研究拟用大鼠进行离子载体类药物马杜霉素的毒性研究,进而探讨牛磺酸对马杜霉素中毒的保护作用,为阐明离子载体类抗球虫药的毒性作用机制提供理论依据。
1、大鼠马杜霉素中毒剂量的筛选:48只SD大鼠,随机分为6组,每组8只,马杜霉素经口单次染毒组的染毒剂量分别为32、16和8mg/kg b.w.;为评价重复染毒对大鼠毒性作用的影响,低剂量组同时分别增设染毒两次和三次剂量组,另设一空白对照组。染毒后除观察一般临床症状外,并于染毒结束后12h处死大鼠,进行眼观组织病理学检查,测定血清、肝脏、心肌、腿肌中丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力,以及血清、肝脏中谷胱甘肽过氧化物酶(GSH-Px)活力。
大鼠马杜霉素中毒临床症状主要表现为厌食、嗜睡、严重者后肢出现麻痹;随染毒剂量的增加,中毒症状加深,严重中毒者出现死亡。剖检变化以肝脏,心肌损伤为主。体内脂质过氧化物含量和过氧化酶活力测定结果表明,马杜霉素中毒能引起大鼠机体脂质过氧化物的含量增加,抗过氧化酶活力下降。随染毒剂量的增加,脂质过氧化损伤加重,呈现一定的剂量-效应关系。重复染毒时,马杜霉素在大鼠具有明显蓄积毒性。综合大鼠临床中毒症状,组织中丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶等测定指标变化及死亡情况,马杜霉素以8mg/kg b.w剂量重复染毒两次较理想。
2、牛磺酸对马杜霉素中毒大鼠的保护作用:40只SD大鼠,随机分为5组,即对照组、马杜霉素染毒组和牛磺酸(Tau)高、中、低三个剂量保护组。Tau各剂量组于染毒前第15d即开始饮水给药,在第15d马杜霉素以8mg/kg b.w.的剂量经口染毒,每天一次,连续染毒2d。染毒期间继续饮用Tau溶液,并在最后一次染毒结束后12h处死所有试验动物,采集血清、肝脏、心肌、腿肌样品。试验观察指标包括:大鼠中毒症状观察、眼观病理学检查,以及血清、肝脏、心肌、腿肌的MDA含量和SOD活力,血清、肝脏的GSH-Px活力的测定。试验结果表明,牛磺酸能降低马杜霉素中毒大鼠体内脂质过氧化物(MDA)含量,显著升高组织SOD活力及血清和肝脏的GSH-Px活力,并呈现一定的剂量-效应关系。当牛磺酸按2%~4%的剂量饮水给药,不仅能减轻大鼠马杜霉素中毒的临床症状,而且对马杜霉素中毒引起的组织损伤具有较好的保护作用。研究结果揭示牛磺酸对马杜霉素所致动物的中毒病可能具有一定防治作用。
Maduramicin is a polyether ionophore antibiotic widely used against coccidiosis in veterinary practice, but it can caused severe toxicosis in domestic animal. Polyether ionophore antibiotic toxicosis is difficulty to diagnosis and no potent detoxicant is available now. The Research goal is to study on maduramicin toxic dose in rats and explore the protective effects of taurine on maduramicin toxicosis.
1. toxic dose by maduramicin in rats: 48 SD rats were randomly divided into six groups, 8 rats in each group. Three dose groups were orally given maduramicin by orally at dose of 32, 16 and 8mg/kg b.w/d respectively, and one control group. The others were two multiple exposd groups in order to evaluate the toxic effect of multiple exposure, which were given maduramicin twice and thrice respectively. The clinical symptoms were observed on maduramicin exposed rats. All the rats were euthanized when rats were administrated 12 hours later, and gross lesions were observed in tissues. SOD and MDA were tested in serum, liver, myocardium and thigh muscle, and GSH-Px was also tested in serum and liver.
With the exposed dose increasing, the clinical symptoms such as anorexia and lethargy became more obvious in exposed rats. The hind limb paralysis or even dead could be observed when rats were seriously in intoxication. Pathological changes were obviously observed in liver and myocardium. The contents of lipid peroxidation production increased and the activity of antiperoxidase decreased after administration in rats, and the lipid peroxidation damage was more serious with the increasing dose of maduramicin. The results of multiple exposures showed that maduramicin has cumulative toxicity. As the clinical intoxicated symptom of rats, the determined index in tissue and the number of dead rats, the fine toxic dose could be induced by maduramicin was administered two times by 8mg/kg b.w in rats.
2. the protective effects of taurine in maduramicin intoxicated rats: 40 SD rats were randomly divided into 5 groups: two contral group, three treatment groups. The rats were adminstered maduramicin at a dose of 8 mg/kg b.w./d for 2 days. Before maduramicin exposure, three treatment groups were orally given at a dose of 1%, 2% and 4% taurine solution for 15 days, and continually given by taurine solution during maduramicin administration. The clinical toxic symptoms were observed after administration of maduramicin. After maduramicin expouse 12 hours later, all rats group were euthanized, and gross tissue lesions were observed. SOD and MDA were tested in serum, liver, myocardium and thigh muscle, and GSH-Px was also tested in serum and liver.
The results showed that taurine could decrease the contents of the lipid peroxidation production, increase the activity of antiperoxidase in maduramicin exposed rats, and relieve the clinical toxic symptoms. The antioxidation effects of taurine were related with dose. The above results suggested that taurine by drinking at doses of 2% ~ 4% could provide good protection for tissue damage induced by maduramicin.
1、大鼠马杜霉素中毒剂量的筛选:48只SD大鼠,随机分为6组,每组8只,马杜霉素经口单次染毒组的染毒剂量分别为32、16和8mg/kg b.w.;为评价重复染毒对大鼠毒性作用的影响,低剂量组同时分别增设染毒两次和三次剂量组,另设一空白对照组。染毒后除观察一般临床症状外,并于染毒结束后12h处死大鼠,进行眼观组织病理学检查,测定血清、肝脏、心肌、腿肌中丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力,以及血清、肝脏中谷胱甘肽过氧化物酶(GSH-Px)活力。
大鼠马杜霉素中毒临床症状主要表现为厌食、嗜睡、严重者后肢出现麻痹;随染毒剂量的增加,中毒症状加深,严重中毒者出现死亡。剖检变化以肝脏,心肌损伤为主。体内脂质过氧化物含量和过氧化酶活力测定结果表明,马杜霉素中毒能引起大鼠机体脂质过氧化物的含量增加,抗过氧化酶活力下降。随染毒剂量的增加,脂质过氧化损伤加重,呈现一定的剂量-效应关系。重复染毒时,马杜霉素在大鼠具有明显蓄积毒性。综合大鼠临床中毒症状,组织中丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶等测定指标变化及死亡情况,马杜霉素以8mg/kg b.w剂量重复染毒两次较理想。
2、牛磺酸对马杜霉素中毒大鼠的保护作用:40只SD大鼠,随机分为5组,即对照组、马杜霉素染毒组和牛磺酸(Tau)高、中、低三个剂量保护组。Tau各剂量组于染毒前第15d即开始饮水给药,在第15d马杜霉素以8mg/kg b.w.的剂量经口染毒,每天一次,连续染毒2d。染毒期间继续饮用Tau溶液,并在最后一次染毒结束后12h处死所有试验动物,采集血清、肝脏、心肌、腿肌样品。试验观察指标包括:大鼠中毒症状观察、眼观病理学检查,以及血清、肝脏、心肌、腿肌的MDA含量和SOD活力,血清、肝脏的GSH-Px活力的测定。试验结果表明,牛磺酸能降低马杜霉素中毒大鼠体内脂质过氧化物(MDA)含量,显著升高组织SOD活力及血清和肝脏的GSH-Px活力,并呈现一定的剂量-效应关系。当牛磺酸按2%~4%的剂量饮水给药,不仅能减轻大鼠马杜霉素中毒的临床症状,而且对马杜霉素中毒引起的组织损伤具有较好的保护作用。研究结果揭示牛磺酸对马杜霉素所致动物的中毒病可能具有一定防治作用。
Maduramicin is a polyether ionophore antibiotic widely used against coccidiosis in veterinary practice, but it can caused severe toxicosis in domestic animal. Polyether ionophore antibiotic toxicosis is difficulty to diagnosis and no potent detoxicant is available now. The Research goal is to study on maduramicin toxic dose in rats and explore the protective effects of taurine on maduramicin toxicosis.
1. toxic dose by maduramicin in rats: 48 SD rats were randomly divided into six groups, 8 rats in each group. Three dose groups were orally given maduramicin by orally at dose of 32, 16 and 8mg/kg b.w/d respectively, and one control group. The others were two multiple exposd groups in order to evaluate the toxic effect of multiple exposure, which were given maduramicin twice and thrice respectively. The clinical symptoms were observed on maduramicin exposed rats. All the rats were euthanized when rats were administrated 12 hours later, and gross lesions were observed in tissues. SOD and MDA were tested in serum, liver, myocardium and thigh muscle, and GSH-Px was also tested in serum and liver.
With the exposed dose increasing, the clinical symptoms such as anorexia and lethargy became more obvious in exposed rats. The hind limb paralysis or even dead could be observed when rats were seriously in intoxication. Pathological changes were obviously observed in liver and myocardium. The contents of lipid peroxidation production increased and the activity of antiperoxidase decreased after administration in rats, and the lipid peroxidation damage was more serious with the increasing dose of maduramicin. The results of multiple exposures showed that maduramicin has cumulative toxicity. As the clinical intoxicated symptom of rats, the determined index in tissue and the number of dead rats, the fine toxic dose could be induced by maduramicin was administered two times by 8mg/kg b.w in rats.
2. the protective effects of taurine in maduramicin intoxicated rats: 40 SD rats were randomly divided into 5 groups: two contral group, three treatment groups. The rats were adminstered maduramicin at a dose of 8 mg/kg b.w./d for 2 days. Before maduramicin exposure, three treatment groups were orally given at a dose of 1%, 2% and 4% taurine solution for 15 days, and continually given by taurine solution during maduramicin administration. The clinical toxic symptoms were observed after administration of maduramicin. After maduramicin expouse 12 hours later, all rats group were euthanized, and gross tissue lesions were observed. SOD and MDA were tested in serum, liver, myocardium and thigh muscle, and GSH-Px was also tested in serum and liver.
The results showed that taurine could decrease the contents of the lipid peroxidation production, increase the activity of antiperoxidase in maduramicin exposed rats, and relieve the clinical toxic symptoms. The antioxidation effects of taurine were related with dose. The above results suggested that taurine by drinking at doses of 2% ~ 4% could provide good protection for tissue damage induced by maduramicin.
引文
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