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LF的急性和亚慢性毒性评估

EVALUATION OF THE ACUTE AND SUBCHRONIC TOXICITY OF L. F.

作者信息

Peng Wen-Jing, Xin Rui-Hua, Luo Yong-Jiang, Liang Ge, Ren Li-Hua, Liu Yan, Wang Gui-Bo, Zheng Ji-Fang

机构信息

Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Key Laboratory of New Animal Drug Project of Gansu Province, Engineering & Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Key Laboratory of Veterinary Pharmaceutics Development, Ministry of Agriculture, Lanzhou 730050, PR China.

Sichuan Animal Science Academy, Chengdu 610066, PR China.

出版信息

Afr J Tradit Complement Altern Med. 2016 Sep 29;13(6):38-53. doi: 10.21010/ajtcam.v13i6.8. eCollection 2016.

Abstract

BACKGROUND

L. f. is used as a traditional Chinese drug to relieve cough and asthma symptoms and to eliminate phlegm. However, L. f. possesses toxicity, and little systematic research has been conducted on its toxic effects in the laboratory.

METHODS AND MATERIALS

The acute group was administered 75% alcohol extract of L. f. in a single dose. A subchronic toxicity study was performed via daily oral administration of L. f. at a dose of 0.34 g/kg body weight in SD rats. The rats were divided into six groups: a petroleum ether extract (PEA) group, an ethyl acetate extract (EEA) group, an n-butyl alcohol extract (NEA) group, a remaining lower aqueous phases (REA) group, a 75% alcohol extract (AEA) group and a control group. Quantitative measurements of cytokines were obtained by fluorescence with a laser scanner using a Cy3 equivalent dye.

RESULTS

The LD of the 75% alcohol extract of L. f. was 15.74 g/kg bw. In the subchronic toxicity study, no significant differences were observed among groups in relative organ weights, urine traits, liver antioxidase levels, or cytokine levels. However, significant sporadic differences were observed in body weight gains, haematology indices, biochemistry values, and histopathology features in PEA, EEA group. In addition, sporadic changes in other groups in measures such as WBC, MCHC, CK, ALP, AST, ALT, LDH, T-BIL, LDL-C, HDL-C, and TC were observed.

CONCLUSION

The toxicity study showed that L. f. can produce toxic effects, mainly on the liver; much less on the heart. The LD was 15.74 g/kg BW in mice, and the subchronic toxicity study, used a dosage of 0.34 g/kg/d.BW, showed that the toxic components of L. f. were mainly concentrated in the petroleum ether fraction, followed by the ethyl acetate fraction, the n-butyl alcohol fraction, the lower aqueous phase and the 75% ethanol extracts. PEA, petroleum ether extract of L. f.; EEA, ethyl acetate extract of L. f.; NEA: n-butyl alcohol extract of L. f.; REA: lower aqueous phases of L. f.; AEA, 75% alcohol extract of L. f.; WBC, white blood cell; RBC, red blood cell, PLT, platelet; HCT, haematocrit; MCV, mean corpuscular volume; HGB, haemoglobin; MCH, mean corpuscular haemoglobin; MCHC, mean corpuscular haemoglobin concentration; CREA, creatinine; LDH, lactate dehydrogenase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; T-BIL, total bilirubin; ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; TP, total protein; ALB, albumin; Glu, glucose; TC, total cholesterol; TG, triglycerides; CK, creatine kinase; GSH, Glutathione; MDA, malondialdehyde; T-SOD, total superoxide dismutase; TNF, tumour necrosis factor; IFN, interferon; MCP, monocyte chemotactic protein C.

摘要

背景

款冬花作为一种传统中药,用于缓解咳嗽、哮喘症状及化痰。然而,款冬花具有毒性,且在实验室中对其毒性作用的系统研究较少。

方法与材料

急性组单次给予款冬花75%乙醇提取物。通过每日对SD大鼠口服给予剂量为0.34 g/kg体重的款冬花进行亚慢性毒性研究。大鼠被分为六组:石油醚提取物(PEA)组、乙酸乙酯提取物(EEA)组、正丁醇提取物(NEA)组、剩余下层水相(REA)组、75%乙醇提取物(AEA)组和对照组。使用Cy3等效染料通过激光扫描仪荧光定量检测细胞因子。

结果

款冬花75%乙醇提取物的半数致死量为15.74 g/kg体重。在亚慢性毒性研究中,各实验组间相对器官重量、尿液性状、肝脏抗氧化酶水平或细胞因子水平未观察到显著差异。然而,在PEA、EEA组中,体重增加、血液学指标、生化值和组织病理学特征出现显著散发性差异。此外,在其他组中也观察到白细胞、平均血红蛋白浓度、肌酸激酶、碱性磷酸酶、天冬氨酸氨基转移酶、丙氨酸氨基转移酶、乳酸脱氢酶、总胆红素、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和总胆固醇等指标的散发性变化。

结论

毒性研究表明,款冬花可产生毒性作用,主要作用于肝脏,对心脏影响较小。小鼠的半数致死量为15.74 g/kg体重,亚慢性毒性研究采用剂量为0.34 g/kg/d体重,结果显示款冬花的毒性成分主要集中在石油醚部位,其次是乙酸乙酯部位、正丁醇部位、下层水相和75%乙醇提取物。PEA,款冬花石油醚提取物;EEA,款冬花乙酸乙酯提取物;NEA:款冬花正丁醇提取物;REA:款冬花下层水相;AEA,款冬花75%乙醇提取物;WBC,白细胞;RBC,红细胞;PLT,血小板;HCT,血细胞比容;MCV,平均红细胞体积;HGB,血红蛋白;MCH,平均红细胞血红蛋白含量;MCHC,平均红细胞血红蛋白浓度;CREA,肌酐;LDH,乳酸脱氢酶;HDL-C,高密度脂蛋白胆固醇;LDL-C,低密度脂蛋白胆固醇;T-BIL,总胆红素;ALT,丙氨酸氨基转移酶;ALP,碱性磷酸酶;AST,天冬氨酸氨基转移酶;TP,总蛋白;ALB,白蛋白;Glu,葡萄糖;TC,总胆固醇;TG,甘油三酯;CK,肌酸激酶;GSH,谷胱甘肽;MDA,丙二醛;T-SOD,总超氧化物歧化酶;TNF,肿瘤坏死因子;IFN;干扰素;MCP,单核细胞趋化蛋白C。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19b7/5412200/7fa4ca7e349c/AJTCAM-13-38-g001.jpg

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