防霉剂脱氢醋酸钠致大鼠出血试验
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摘要
脱氢醋酸钠作为防霉剂已广泛应用于食品、饲料及化妆品等多个领域,但有关脱氢醋酸钠使用后,引起动物组织出血的报道极少。通过灌胃给予Wistar大鼠50、100、150、200mg/kg脱氢醋酸钠,连续12d,对照组灌胃生理盐水。在灌胃后不同时间测定大鼠体重、饲料消耗、凝血酶原时间(PT)和活化部分凝血酶原时间(APTT),并对主要脏器进行组织病理学观察。结果表明,150mg/kg和200mg/kg组灌胃3d后,大鼠体重和饲料消耗与对照组相比显著降低(P<0.05);50mg/kg和100mg/kg组则在7d~10d后,显著低于对照组(P<0.05)。试验期内雌鼠增重远远小于雄鼠。给予脱氢醋酸钠后,所测时间点的PT、APTT值均极显著高于正常对照组(P<0.01),雌雄大鼠间APTT值有明显差异。雌性大鼠的APTT值随剂量、时间的增加而延长。组织切片检查心、肝、脾、肺、肾存在不同程度的出血,肝和肾组织出血较明显。结果表明,较大剂量脱氢醋酸钠可致大鼠凝血功能障碍,能引起主要脏器不同程度出血的倾向。作为食品或饲料添加剂使用,使用高剂量脱氢醋酸钠时,存在一定的安全风险。
Sodium dehydroacetate is widely used in foods,feed and cosmetics etc.as an antifungal additive,but little information is focused on its anticoagulation.Wistar rats were given with a gavage of sodium dehydroacetate once a day for 12 dat doses of 50,100,150 and 200 mg/kg,and saline as a control.The body weight,feed consumption,prothrombin time(PT)and activated partial thromboplastin time(APTT)were measured at different time post administration.Histopathological analysis was mead for main tissues.The results showed that the body weight and feed consumption in 150 and 200 mg/kg at 3 dpost administration were significantly lower than that in control,whereas those in 50 and 100 mg/kg at 7 d-10 dpost administration were significantly lower than that in control(P<0.05).The weight gain of female rats was lower than that of male in whole test time period.The values of PT,APTT in groups treated by sodium dehydroacetiate were extremely higher than that in control at experimental period(P<0.01).There were clearly differences between female and male in APTT data,which the value of APTT in female increased with increasing of dose and exposure time of sodium dehydroacetate.Some extent hemorrages in heart,liver,spleen,lung and kidney tissues were observed in histopathological analysis.The results showed that coagulation diaorders or varying degrees of hemorrages in main organs may be induced by high dose sodium dehydroacetate,implying safety risk on human and animals when it is used as a food or feed additive.
Sodium dehydroacetate is widely used in foods,feed and cosmetics etc.as an antifungal additive,but little information is focused on its anticoagulation.Wistar rats were given with a gavage of sodium dehydroacetate once a day for 12 dat doses of 50,100,150 and 200 mg/kg,and saline as a control.The body weight,feed consumption,prothrombin time(PT)and activated partial thromboplastin time(APTT)were measured at different time post administration.Histopathological analysis was mead for main tissues.The results showed that the body weight and feed consumption in 150 and 200 mg/kg at 3 dpost administration were significantly lower than that in control,whereas those in 50 and 100 mg/kg at 7 d-10 dpost administration were significantly lower than that in control(P<0.05).The weight gain of female rats was lower than that of male in whole test time period.The values of PT,APTT in groups treated by sodium dehydroacetiate were extremely higher than that in control at experimental period(P<0.01).There were clearly differences between female and male in APTT data,which the value of APTT in female increased with increasing of dose and exposure time of sodium dehydroacetate.Some extent hemorrages in heart,liver,spleen,lung and kidney tissues were observed in histopathological analysis.The results showed that coagulation diaorders or varying degrees of hemorrages in main organs may be induced by high dose sodium dehydroacetate,implying safety risk on human and animals when it is used as a food or feed additive.
引文
[1]候立娟,林金盛,方东璐,等.脱氢醋酸钠对草菇外观品质和保护酶活性的影响[J].江苏农业学报,2014,30(6):1484-1489.
[2]Yan Q Q,Zhang J L,Dong H Z,et al.Properties and antimicrobial activities of starch-sodium alginate composite films incorporated with sodium dehydroacetate or rosemary extract[J].J Appl Polym Sci,2013,127(3):1951-1958.
[3]屈长波,李博,张莉莉,等.高剂量脱氢醋酸钠对断奶仔猪生长性能血清生化指标和血常规指标的影响[J].动物营养学报,2015,27(3):878-884.
[4]段会轲,周辉.脱氢醋酸钠复合保鲜在低温肉食品中的应用[J].肉类工业,2008(9):14-16.
[5]屈长波,孙得发,王恬.饲料破坏法研究脱氢醋酸钠的防霉效果[J].饲料工业,2014,17(35):102-103.
[6]侯立娟,林金盛,方东路,等.脱氢醋酸钠对草菇外观品质和保护酶活性的影响[J].江苏农业学报,2014,30(6):1484-1489.
[7]Spencer H C,Rowe V K,McCollister D D.Dehydroacetic acid(DHA).Ⅰ.Acute and chronic toxicity[J].J Pharmacol Exp Therap,1950,99:57-68.
[8]Sakaguchi Y,Suga S,Oshida K,et al.Anticoagulant effect of sodium dehydroacetate(DHA-S)in rats[J].J Appl Toxicol,2008,28:524-529.
[9]Foti C,Antelmi A,Guida S,et al.Sodium dehydroacetate:An emerging allergen[J].Dermat,2012,23(5):243-243.
[10]Foti C,Romita P,Ettorre G,et al.Allergic contact dermatitis caused by resorcinol and sodiumdehydroacetate in a patient with leg ulcers[J].Contact Dermat,2016,74(6):383-384.
[11]Milpied B,Collet E,Genillier N,et al.Allergic contact dermatitis caused by sodium dehydroacetate,not hyaluronic acid,in Ialuset(R)cream[J].Contact Dermat,2011,65(6):359-360.
[12]Yamashoji S,Isshiki K.Rapid detection of cytotoxicity of food additives and contaminants by a novel cytotoxicity test,menadione-catalyzed H2O2 production assay[J].Cytotechnology,2001,37:171-178.
[13]Priputina L S,Ingre V G,Ol'shevskaya O D,et al.Experimental study on the possible use of dehydroacetic acid sodium salt as a food additive[J].Voprosy Pitaniya,1987,5:50-53.
[14]GB2760—2014.食品添加剂使用标准[S].
[15]Acid D.Final report on the safety assessment of sodium dehydroacetate and dehydroacetic acid[J].Int J Toxicol,1985,4(3):123-159.
[16]Uchida O,Naito K,Yasuhara K,et al.Studies on the acute oral toxicity of dehydroacetic acid,sorbic acid and their combination compound in rats[J].Bull Nat Ins Hyg Sci,1985,103:166-171.
[2]Yan Q Q,Zhang J L,Dong H Z,et al.Properties and antimicrobial activities of starch-sodium alginate composite films incorporated with sodium dehydroacetate or rosemary extract[J].J Appl Polym Sci,2013,127(3):1951-1958.
[3]屈长波,李博,张莉莉,等.高剂量脱氢醋酸钠对断奶仔猪生长性能血清生化指标和血常规指标的影响[J].动物营养学报,2015,27(3):878-884.
[4]段会轲,周辉.脱氢醋酸钠复合保鲜在低温肉食品中的应用[J].肉类工业,2008(9):14-16.
[5]屈长波,孙得发,王恬.饲料破坏法研究脱氢醋酸钠的防霉效果[J].饲料工业,2014,17(35):102-103.
[6]侯立娟,林金盛,方东路,等.脱氢醋酸钠对草菇外观品质和保护酶活性的影响[J].江苏农业学报,2014,30(6):1484-1489.
[7]Spencer H C,Rowe V K,McCollister D D.Dehydroacetic acid(DHA).Ⅰ.Acute and chronic toxicity[J].J Pharmacol Exp Therap,1950,99:57-68.
[8]Sakaguchi Y,Suga S,Oshida K,et al.Anticoagulant effect of sodium dehydroacetate(DHA-S)in rats[J].J Appl Toxicol,2008,28:524-529.
[9]Foti C,Antelmi A,Guida S,et al.Sodium dehydroacetate:An emerging allergen[J].Dermat,2012,23(5):243-243.
[10]Foti C,Romita P,Ettorre G,et al.Allergic contact dermatitis caused by resorcinol and sodiumdehydroacetate in a patient with leg ulcers[J].Contact Dermat,2016,74(6):383-384.
[11]Milpied B,Collet E,Genillier N,et al.Allergic contact dermatitis caused by sodium dehydroacetate,not hyaluronic acid,in Ialuset(R)cream[J].Contact Dermat,2011,65(6):359-360.
[12]Yamashoji S,Isshiki K.Rapid detection of cytotoxicity of food additives and contaminants by a novel cytotoxicity test,menadione-catalyzed H2O2 production assay[J].Cytotechnology,2001,37:171-178.
[13]Priputina L S,Ingre V G,Ol'shevskaya O D,et al.Experimental study on the possible use of dehydroacetic acid sodium salt as a food additive[J].Voprosy Pitaniya,1987,5:50-53.
[14]GB2760—2014.食品添加剂使用标准[S].
[15]Acid D.Final report on the safety assessment of sodium dehydroacetate and dehydroacetic acid[J].Int J Toxicol,1985,4(3):123-159.
[16]Uchida O,Naito K,Yasuhara K,et al.Studies on the acute oral toxicity of dehydroacetic acid,sorbic acid and their combination compound in rats[J].Bull Nat Ins Hyg Sci,1985,103:166-171.