磺胺喹噁啉对小鼠和鸡的毒性研究
摘要
本研究以小鼠为试验动物,复制出小鼠磺胺喹噁啉中毒模型,观察其中毒症状,免疫功能的改变以及病理学变化。在此基础上,研究了磺胺喹噁啉对鸡的毒性,为磺胺喹噁啉在兽医临床上的合理应用和中毒防治提供试验依据。
1.磺胺喹噁啉对小鼠的毒性试验
以改良寇氏法测定磺胺喹噁啉对小鼠的急性毒性—LD50。将50只小鼠,随机分为5组,每组10只,雌雄各半。Ⅰ～Ⅳ组为实验组,Ⅴ组为对照组。Ⅰ～Ⅳ组每只分别灌服磺胺喹噁啉70 mg/kg,140 mg/kg,210 mg/kg和280 mg/kg,第Ⅴ组灌服等量生理盐水作为对照。隔天给药一次,连续7次。观察小鼠灌服不同剂量磺胺喹噁啉后的临床症状。试验结束前6～8 h给小鼠腹腔注射5%鸡红细胞悬液,测定小鼠腹腔巨噬细胞吞噬鸡红细胞的吞噬活性。剖杀小鼠,测定心、肝、肾、脾等脏器的质量(g)并与其体重(kg)比较,即得脏器指数。剖杀后,对主要脏器进行大体剖检观察,对病变明显的脏器进行石蜡切片观察。结果表明,磺胺喹噁啉对小鼠口服的LD50为4 889.90 mg/kg,95%可信限为5 471.71～4 308.09 mg/kg,属于低毒化合物。随着小鼠灌服磺胺喹噁啉剂量的增加和试验时间的推移,小鼠的中毒症状明显加重。小鼠巨噬细胞吞噬鸡红细胞的能力随着剂量的增大而降低,即小鼠非特异性免疫功能活性降低。小鼠的脾脏指数和心脏指数随着剂量的增大而降低,说明小鼠的免疫功能受到抑制,心脏功能受到一定损害。小鼠的肝脏指数和肾脏指数随着剂量的增大而增大,说明肝肾功能也受到损害。病理解剖观察发现,肝肾有明显肿大,脾脏肿胀且颜色略有加深,淤血,心脏的心包液增多。病理组织学观察发现,心肌纤维肿胀,变性;脾窦扩张充血,巨细胞增多,毛细血管扩张;肾脏皮质区肾小管上皮细胞肿胀变性,肾小球囊腔扩张,血管球萎缩。
2.磺胺喹噁啉对鸡的毒性试验
以改良寇氏法进行磺胺喹噁啉对鸡的急性毒性—LD50测定。将40只鸡随机分为4组,每组10只,雌雄各半。Ⅰ～Ⅲ组为实验组,Ⅳ组为对照组。Ⅰ～Ⅲ组每只分别灌服磺胺喹噁啉90 mg/kg,120 mg/kg和150 mg/kg,第Ⅳ组灌服等量生理盐水作为对照。每天灌服一次,连续2周。观察鸡灌服不同剂量磺胺喹噁啉后的临床症状。每周每组静脉采血10 mL/只,其中3 mL加抗凝用于用于血细胞计数、活淋巴细胞和高铁血红蛋白百分率的测定,7 mL用于血凝时间和分离血清测定生理生化指标。正常饲喂至第7周,剖杀所有鸡只,测定其心、肝、脾、肾等脏器的脏器指数。剖杀后,对主要脏器进行大体剖检观察,对病变明显的脏器进行石蜡切片观察。结果表明,磺胺喹噁啉对鸡口服的LD50为12122.05mg/kg,95%可信限为15570.87~9437.11mg/kg,属于实际无毒化合物。随着鸡灌服磺胺喹噁啉剂量的增加和试验时间的推移,鸡的中毒症状明显加重;实验组鸡只红细胞和白细胞的数量减少,血凝时间延长,高铁血红蛋白百分率增加,活淋巴细胞的百分率降低,鸡的心脏指数和脾脏指数随着剂量的增大而降低,说明鸡的免疫功能受到抑制,心脏功能受到一定损害。尿素氮和肌酐的含量增加,丙氨酸氨基转移酶和门冬氨酸氨基转移酶活性增高,鸡的肝脏指数和肾脏指数随着剂量的增大而增大,说明肝肾功能也受到损害。病理解剖观察发现,心脏色泽不均;肝脏略微肿胀;脾脏体积增大;肾脏稍肿大。病理组织学观察发现,心肌纤维肿胀,部分坏死;肝窦隙可见大量红细胞和少量淋巴细胞浸润;脾窦扩张充血,脾小体萎缩或消失;肾间质血管扩张、充血,有单核细胞、淋巴细胞等浸润。
综上所述,磺胺喹噁啉对受试动物的心脏、肝脏、脾脏和肾脏等脏器有损害作用,临床症状明显,免疫活性降低,病理学检查病变显著,呈一定的剂量—反应依赖关系。
Mice were used applied as experimental animals, and Sulfaquinoxaline (SQ) poisoning model was replicated, toxic symptoms, changes of immune function and pathology were observed. Based on these, toxicity of SQ on chickens was researched in order to applicate SQ reasonably in veterinary clinic and provide test basis for poisoning protection and treatment. 1. Subacute toxicity test of SQ on mice
Acute toxicity—LD50 of SQ to mice was determined by modified Karber method. 50 mices were randomly allocated into 5 groups with 10 each, and half male and half female. GroupⅠ~Ⅳwere treated as experimental group, while groupⅤas control. GroupⅠ~Ⅳwere gavaged with SQ solution 70 mg / kg,140 mg / kg, 210 mg / kg and 280 mg / kg respectively, and groupⅤwere gavaged with the same dose of normal saline as control for 7 times every two days. Clinic symptoms were observed after mice were gavaged with different doses of SQ solutions. After experiment was finished 6 to 8 hours, all were injected with 5% CRBC suspension intraperitoneally, activity of macrophage were determined. Then mice were killed, and weights of hearts, livers, kidenies, spleens and other organs were compared with the body weights in order to compute the organ indices. Main organs were detected, for the organs with obvious pathological changes, paraffin sections observations were performed. The results showed that LD50 to mice by oral administration was 12122.05 mg/kg, and 95% confidence limit was 15570.87~9437.11 mg/kg. As dose increased and time went by, poisoning symptoms were obviously aggravated. Activity of macrophage’s phagocytosing RBC of chicken decresed while dose increased, which means non-specific immune functional activity was dropped. Spleen index and heart index were decreased as dose increased, which means immune function of mice were inhibited, and heart function were harmed in certain extent. Liver index and kidney index were increased, which means functions of livers and kidneys were damaged. Livers and kidneys were obviously enlarged, colors of spleen were deeper slightly and congested and pericardial fluid increased in pathological anatomy. Myocardial fiber were swelled and degenerated, splenic sinus congested and dilated, giant corpuscle increased, capillary swelled, cellula epithelialis of nephric tubule in kidney cortical area degenerated, capsula glomeruli expanded and glomerulus shrinked in pathology histological observation.
2. Sulfaquinoxaline in chicken toxicity test
Acute toxicity—LD50 of SQ to chicken were determined by modified Karber method. 40 mices were randomly allocated into 4 groups with 10 each and half male and half female. GroupⅠ~Ⅲwere treated as experimental group, while groupⅣas control. GroupⅠ~Ⅲwere gavaged with SQ solution 90 mg / kg,120 mg / kg, and 150 mg / kg respectively, and groupⅣwere gavaged with the same dose of normal saline as control for two weeks every day. Clinic symptoms were observed after chickens were gavaged with different doses of SQ solutions. Blood sampling were performed in each group from vein for 10 mL every week, 6 mL were anticoagulated for blood count, hemagglutination time, percentages determination of lymph cell and ferrihemoglobin, the rest 4 mL for serum separation and physiological and biochemical indices determination. All were killed 7 weeks later, whose weight of hearts, livers, spleens, kidneies and other organs were compared with the body weights to calculate the organ indices. After that, paraffin sections observations of main organs were performed. The results showed that SQ ranked in actually non-toxic grade, whose LD50 to chicken by oral administration was 4889.90 mg/kg, and 95% confidence limit was 5471.71~4308.09 mg/kg. As dose increased and time went by, poisoning symptoms were obviously aggravated. RBC and WBC decresed, hemagglutinin time extended, ferrihemoglobin increased, percentage of living lymph cell decreased. Spleen index and heart index were decreased as dose increased, which means immune function of chicken were inhibited, and heart function were harmed in certain extent. Content of urea nitrogen and creatinine increased, and activity of alanine aminotransferase and aspartic acid increased. Liver index and kidney index were increased, which means functions of livers and kidneys were damaged. Livers and kidneys were obviously enlarged, color of heart was uneven, livers expanded slightly, spleen enlarged, kidneies enlarged slightly. Myocardial fiber were swelled and parts degenerated, a plenty of RBCs and a few lymph cells infiltrated in splenic sinus, sinus lienis swelled and congested, acinus lienalis shrinked or disappeared, and blood vesselsof renal interstitium swelled and congested with histoleucocytes and lymph cells infiltrated.
In a word, SQ damaged heart, liver, spleen, kidney and other organs of trial animal with obvious clinic symptoms, immune activity dropping, and obvious pathological changes which depended on dose-reaction.
1.磺胺喹噁啉对小鼠的毒性试验
以改良寇氏法测定磺胺喹噁啉对小鼠的急性毒性—LD50。将50只小鼠,随机分为5组,每组10只,雌雄各半。Ⅰ～Ⅳ组为实验组,Ⅴ组为对照组。Ⅰ～Ⅳ组每只分别灌服磺胺喹噁啉70 mg/kg,140 mg/kg,210 mg/kg和280 mg/kg,第Ⅴ组灌服等量生理盐水作为对照。隔天给药一次,连续7次。观察小鼠灌服不同剂量磺胺喹噁啉后的临床症状。试验结束前6～8 h给小鼠腹腔注射5%鸡红细胞悬液,测定小鼠腹腔巨噬细胞吞噬鸡红细胞的吞噬活性。剖杀小鼠,测定心、肝、肾、脾等脏器的质量(g)并与其体重(kg)比较,即得脏器指数。剖杀后,对主要脏器进行大体剖检观察,对病变明显的脏器进行石蜡切片观察。结果表明,磺胺喹噁啉对小鼠口服的LD50为4 889.90 mg/kg,95%可信限为5 471.71～4 308.09 mg/kg,属于低毒化合物。随着小鼠灌服磺胺喹噁啉剂量的增加和试验时间的推移,小鼠的中毒症状明显加重。小鼠巨噬细胞吞噬鸡红细胞的能力随着剂量的增大而降低,即小鼠非特异性免疫功能活性降低。小鼠的脾脏指数和心脏指数随着剂量的增大而降低,说明小鼠的免疫功能受到抑制,心脏功能受到一定损害。小鼠的肝脏指数和肾脏指数随着剂量的增大而增大,说明肝肾功能也受到损害。病理解剖观察发现,肝肾有明显肿大,脾脏肿胀且颜色略有加深,淤血,心脏的心包液增多。病理组织学观察发现,心肌纤维肿胀,变性;脾窦扩张充血,巨细胞增多,毛细血管扩张;肾脏皮质区肾小管上皮细胞肿胀变性,肾小球囊腔扩张,血管球萎缩。
2.磺胺喹噁啉对鸡的毒性试验
以改良寇氏法进行磺胺喹噁啉对鸡的急性毒性—LD50测定。将40只鸡随机分为4组,每组10只,雌雄各半。Ⅰ～Ⅲ组为实验组,Ⅳ组为对照组。Ⅰ～Ⅲ组每只分别灌服磺胺喹噁啉90 mg/kg,120 mg/kg和150 mg/kg,第Ⅳ组灌服等量生理盐水作为对照。每天灌服一次,连续2周。观察鸡灌服不同剂量磺胺喹噁啉后的临床症状。每周每组静脉采血10 mL/只,其中3 mL加抗凝用于用于血细胞计数、活淋巴细胞和高铁血红蛋白百分率的测定,7 mL用于血凝时间和分离血清测定生理生化指标。正常饲喂至第7周,剖杀所有鸡只,测定其心、肝、脾、肾等脏器的脏器指数。剖杀后,对主要脏器进行大体剖检观察,对病变明显的脏器进行石蜡切片观察。结果表明,磺胺喹噁啉对鸡口服的LD50为12122.05mg/kg,95%可信限为15570.87~9437.11mg/kg,属于实际无毒化合物。随着鸡灌服磺胺喹噁啉剂量的增加和试验时间的推移,鸡的中毒症状明显加重;实验组鸡只红细胞和白细胞的数量减少,血凝时间延长,高铁血红蛋白百分率增加,活淋巴细胞的百分率降低,鸡的心脏指数和脾脏指数随着剂量的增大而降低,说明鸡的免疫功能受到抑制,心脏功能受到一定损害。尿素氮和肌酐的含量增加,丙氨酸氨基转移酶和门冬氨酸氨基转移酶活性增高,鸡的肝脏指数和肾脏指数随着剂量的增大而增大,说明肝肾功能也受到损害。病理解剖观察发现,心脏色泽不均;肝脏略微肿胀;脾脏体积增大;肾脏稍肿大。病理组织学观察发现,心肌纤维肿胀,部分坏死;肝窦隙可见大量红细胞和少量淋巴细胞浸润;脾窦扩张充血,脾小体萎缩或消失;肾间质血管扩张、充血,有单核细胞、淋巴细胞等浸润。
综上所述,磺胺喹噁啉对受试动物的心脏、肝脏、脾脏和肾脏等脏器有损害作用,临床症状明显,免疫活性降低,病理学检查病变显著,呈一定的剂量—反应依赖关系。
Mice were used applied as experimental animals, and Sulfaquinoxaline (SQ) poisoning model was replicated, toxic symptoms, changes of immune function and pathology were observed. Based on these, toxicity of SQ on chickens was researched in order to applicate SQ reasonably in veterinary clinic and provide test basis for poisoning protection and treatment. 1. Subacute toxicity test of SQ on mice
Acute toxicity—LD50 of SQ to mice was determined by modified Karber method. 50 mices were randomly allocated into 5 groups with 10 each, and half male and half female. GroupⅠ~Ⅳwere treated as experimental group, while groupⅤas control. GroupⅠ~Ⅳwere gavaged with SQ solution 70 mg / kg,140 mg / kg, 210 mg / kg and 280 mg / kg respectively, and groupⅤwere gavaged with the same dose of normal saline as control for 7 times every two days. Clinic symptoms were observed after mice were gavaged with different doses of SQ solutions. After experiment was finished 6 to 8 hours, all were injected with 5% CRBC suspension intraperitoneally, activity of macrophage were determined. Then mice were killed, and weights of hearts, livers, kidenies, spleens and other organs were compared with the body weights in order to compute the organ indices. Main organs were detected, for the organs with obvious pathological changes, paraffin sections observations were performed. The results showed that LD50 to mice by oral administration was 12122.05 mg/kg, and 95% confidence limit was 15570.87~9437.11 mg/kg. As dose increased and time went by, poisoning symptoms were obviously aggravated. Activity of macrophage’s phagocytosing RBC of chicken decresed while dose increased, which means non-specific immune functional activity was dropped. Spleen index and heart index were decreased as dose increased, which means immune function of mice were inhibited, and heart function were harmed in certain extent. Liver index and kidney index were increased, which means functions of livers and kidneys were damaged. Livers and kidneys were obviously enlarged, colors of spleen were deeper slightly and congested and pericardial fluid increased in pathological anatomy. Myocardial fiber were swelled and degenerated, splenic sinus congested and dilated, giant corpuscle increased, capillary swelled, cellula epithelialis of nephric tubule in kidney cortical area degenerated, capsula glomeruli expanded and glomerulus shrinked in pathology histological observation.
2. Sulfaquinoxaline in chicken toxicity test
Acute toxicity—LD50 of SQ to chicken were determined by modified Karber method. 40 mices were randomly allocated into 4 groups with 10 each and half male and half female. GroupⅠ~Ⅲwere treated as experimental group, while groupⅣas control. GroupⅠ~Ⅲwere gavaged with SQ solution 90 mg / kg,120 mg / kg, and 150 mg / kg respectively, and groupⅣwere gavaged with the same dose of normal saline as control for two weeks every day. Clinic symptoms were observed after chickens were gavaged with different doses of SQ solutions. Blood sampling were performed in each group from vein for 10 mL every week, 6 mL were anticoagulated for blood count, hemagglutination time, percentages determination of lymph cell and ferrihemoglobin, the rest 4 mL for serum separation and physiological and biochemical indices determination. All were killed 7 weeks later, whose weight of hearts, livers, spleens, kidneies and other organs were compared with the body weights to calculate the organ indices. After that, paraffin sections observations of main organs were performed. The results showed that SQ ranked in actually non-toxic grade, whose LD50 to chicken by oral administration was 4889.90 mg/kg, and 95% confidence limit was 5471.71~4308.09 mg/kg. As dose increased and time went by, poisoning symptoms were obviously aggravated. RBC and WBC decresed, hemagglutinin time extended, ferrihemoglobin increased, percentage of living lymph cell decreased. Spleen index and heart index were decreased as dose increased, which means immune function of chicken were inhibited, and heart function were harmed in certain extent. Content of urea nitrogen and creatinine increased, and activity of alanine aminotransferase and aspartic acid increased. Liver index and kidney index were increased, which means functions of livers and kidneys were damaged. Livers and kidneys were obviously enlarged, color of heart was uneven, livers expanded slightly, spleen enlarged, kidneies enlarged slightly. Myocardial fiber were swelled and parts degenerated, a plenty of RBCs and a few lymph cells infiltrated in splenic sinus, sinus lienis swelled and congested, acinus lienalis shrinked or disappeared, and blood vesselsof renal interstitium swelled and congested with histoleucocytes and lymph cells infiltrated.
In a word, SQ damaged heart, liver, spleen, kidney and other organs of trial animal with obvious clinic symptoms, immune activity dropping, and obvious pathological changes which depended on dose-reaction.
引文
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