酒石酸长春瑞滨胶束重复给药对Beagle犬肝、肾毒性研究
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摘要
目的研究长期重复给予注射用酒石酸长春瑞滨胶束(NVB-m)对Beagle犬肝、肾毒性的影响,同时设同类市售注射用酒石酸长春瑞滨(NVB)进行毒性比较研究。方法 Beagle犬48只,按体质量、性别随机分为对照组、空白胶束组、NVB组和NVB-m 6、12、24 mg/m~2组,每组8只。NVB组给予24 mg/m~2剂量的NVB,空白胶束组给予相同浓度的空白胶束,对照组给予生理盐水,静脉给药。进行一般状态观察,称取Beagle犬体质量,取血检测血清生化指标,采集尿液检测尿常规,大体解剖称量肝、肾质量,计算脏器系数并做组织病理学检查。结果一般症状检查可见,NVB组、NVB-m 12、24 mg/m~2组在给药期间有食欲不振、食量减少甚至拒食等症状,随给药次数增加而减轻。动物体质量在试验期间未见明显异常。血清生化检查可见,与对照组比较,给药期间NVB组及NVB-m 6、12、24 mg/m~2组天冬氨酸转氨酶(AST)、天冬氨酸转氨酶(ALT)、总胆红素(TBIL)升高,总蛋白(TP)、白蛋白(ALB)降低,其中NVB-m 24 mg/m~2组对动物TP影响较NVB组轻微;NVB组及NVB-m 24 mg/m~2组动物ALT升高(部分组别部分时间差异显著P<0.05、0.01),恢复期可恢复正常。尿生化检查、大体解剖及脏器质量检查、组织病理学检查未见明显异常。结论 NVB-m长期给药对Beagle犬有轻微肝毒性,主要表现为肝功指标异常;NVB-m对Beagle犬无肾毒性;NVB-m与NVB没有明显肝、肾毒性差异。
Objective To research the effect of repeated intravenous injection of vinorelbine tartrate micelles for injection(NVB-m)on hepatotoxicity and nephrotoxicity of Beagle dogs. At the same time, a comparative study on the toxicity of marketed vinorelbine tartrate for injection(NVB) was conducted.Methods 48 Beagle dogs were randomly divided into physiological control group, blank micelle group, market control group(NVB) and NVB-m 6, 12, 24 mg/m~2 dose group, with 8 dogs in each group. The market control group was given 24 mg/m~2 dose of NVB. The blank micelle group was given the same concentration of blank micelles as the drug group. Physiological saline was given to the physiological control group, intravenous administration. Beagle dogs were weighed,blood biochemical indexes were detected, urine routine was detected, liver and kidney weights were measured with gross anatomy,organ coefficient was calculated and histopathological examination was done. Results General symptoms test showed that NVB group, NVB-m 12, 24 mg/m~2 group had symptoms such as loss of appetite, decreased food intake and even antifeeding during the course of administration, which were alleviated with the increase of dosage times. There was no obvious abnormality in body weight during the experiment. Blood biochemical examination showed that AST, ALP, TBIL increased, TP and ALB decreased in NVB group and NVB-m 6, 12, 24 mg/m~2 group, of which NVB-m 24 mg/m~2 group had slight effect on TP, NVB group and NVB-m 24 mg/m~2 group could increase ALT. Urine biochemical examination, gross anatomy and viscera weight examination, histopathological examination showed no obvious abnormality. Conclusions NVB-m had slight hepatotoxicity to Beagle dogs, mainly showing abnormal liver function index; NVB-m had no nephrotoxicity to Beagle dogs; NVB-m and NVB had no significant difference in hepatotoxicity and nephrotoxicity.
Objective To research the effect of repeated intravenous injection of vinorelbine tartrate micelles for injection(NVB-m)on hepatotoxicity and nephrotoxicity of Beagle dogs. At the same time, a comparative study on the toxicity of marketed vinorelbine tartrate for injection(NVB) was conducted.Methods 48 Beagle dogs were randomly divided into physiological control group, blank micelle group, market control group(NVB) and NVB-m 6, 12, 24 mg/m~2 dose group, with 8 dogs in each group. The market control group was given 24 mg/m~2 dose of NVB. The blank micelle group was given the same concentration of blank micelles as the drug group. Physiological saline was given to the physiological control group, intravenous administration. Beagle dogs were weighed,blood biochemical indexes were detected, urine routine was detected, liver and kidney weights were measured with gross anatomy,organ coefficient was calculated and histopathological examination was done. Results General symptoms test showed that NVB group, NVB-m 12, 24 mg/m~2 group had symptoms such as loss of appetite, decreased food intake and even antifeeding during the course of administration, which were alleviated with the increase of dosage times. There was no obvious abnormality in body weight during the experiment. Blood biochemical examination showed that AST, ALP, TBIL increased, TP and ALB decreased in NVB group and NVB-m 6, 12, 24 mg/m~2 group, of which NVB-m 24 mg/m~2 group had slight effect on TP, NVB group and NVB-m 24 mg/m~2 group could increase ALT. Urine biochemical examination, gross anatomy and viscera weight examination, histopathological examination showed no obvious abnormality. Conclusions NVB-m had slight hepatotoxicity to Beagle dogs, mainly showing abnormal liver function index; NVB-m had no nephrotoxicity to Beagle dogs; NVB-m and NVB had no significant difference in hepatotoxicity and nephrotoxicity.
引文
[1] Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes:ten-year results[J]. JAMA, 1995, 273(7):542-547.
[2] Okouneva T, Hill B T, Wilson L, et al. The effects of vinflunine, vinorelbine and vinblastine on centromere dynamics[J]. Mol Cancer Ther, 2003, 2(5):427-436.
[3] Depierre A, Lemarie E, Dabouis G, et al.A phase II study of Navelbine(vinorelbine)in the treatment of non-smallcell lung cancer[J]. Am J Clin Oncol, 1991, 14(2):115-119.
[4] Loo W T, Sasano H, Chow L W. Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues[J]. Biomed Pharmacother, 2007, 61(9):596-600.
[5]马继敏.长春瑞滨联合顺铂治疗复发性卵巢癌的临床疗效[J].中外健康文摘, 2009, 6(22):47-49.
[6]尹序德,周澄亚,陈晶,等.长春瑞滨联合多西紫杉醇治疗晚期食管癌疗效观察[J].中国基层医药, 2009, 16(8):1490-1491.
[7]潘险峰,徐炎华.奈达铂联合长春瑞滨治疗晚期头颈部恶性肿瘤67例疗效分析[J].长江大学学报:自然科学版, 2008, 5(3):29-30.
[8]陈洁,董戴玉,杨镜明.长春瑞滨为主的联合方案治疗恶性淋巴瘤临床观察[J].中华肿瘤防治杂志, 2003, 10(2):201-202.
[9] Yoh K, Niho S, Goto K, et al. Randomized trial of drip infusion versus bolus injection of vinorelbine for the control of local venous toxicity[J]. Lung Cancer, 2007,55(3):337-341.
[10]张代钊.化疗副反应的中西医治疗--肝胆毒性、肾脏毒性[J].东方药膳, 2010(7):26-28.
[11]细胞毒类抗肿瘤药物非临床研究技术指导原则[S].2006.
[11]胡玉海.血肌酐、血尿素氮评价慢性肾脏病患者肾功能时与年龄的相关性研究[J].国际检验医学杂志,2013, 34(10):1313-1314.
[2] Okouneva T, Hill B T, Wilson L, et al. The effects of vinflunine, vinorelbine and vinblastine on centromere dynamics[J]. Mol Cancer Ther, 2003, 2(5):427-436.
[3] Depierre A, Lemarie E, Dabouis G, et al.A phase II study of Navelbine(vinorelbine)in the treatment of non-smallcell lung cancer[J]. Am J Clin Oncol, 1991, 14(2):115-119.
[4] Loo W T, Sasano H, Chow L W. Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues[J]. Biomed Pharmacother, 2007, 61(9):596-600.
[5]马继敏.长春瑞滨联合顺铂治疗复发性卵巢癌的临床疗效[J].中外健康文摘, 2009, 6(22):47-49.
[6]尹序德,周澄亚,陈晶,等.长春瑞滨联合多西紫杉醇治疗晚期食管癌疗效观察[J].中国基层医药, 2009, 16(8):1490-1491.
[7]潘险峰,徐炎华.奈达铂联合长春瑞滨治疗晚期头颈部恶性肿瘤67例疗效分析[J].长江大学学报:自然科学版, 2008, 5(3):29-30.
[8]陈洁,董戴玉,杨镜明.长春瑞滨为主的联合方案治疗恶性淋巴瘤临床观察[J].中华肿瘤防治杂志, 2003, 10(2):201-202.
[9] Yoh K, Niho S, Goto K, et al. Randomized trial of drip infusion versus bolus injection of vinorelbine for the control of local venous toxicity[J]. Lung Cancer, 2007,55(3):337-341.
[10]张代钊.化疗副反应的中西医治疗--肝胆毒性、肾脏毒性[J].东方药膳, 2010(7):26-28.
[11]细胞毒类抗肿瘤药物非临床研究技术指导原则[S].2006.
[11]胡玉海.血肌酐、血尿素氮评价慢性肾脏病患者肾功能时与年龄的相关性研究[J].国际检验医学杂志,2013, 34(10):1313-1314.