Acute Toxicity of Huoxin Pills in Mice

doi:10.19803/j.1672-8629.2021.10.06

Abstract

Abstract: Objective To investigate the acute toxicity of Huoxin pills in mice. Methods The maximum tolerance dose (MTD) test was chosen due to the unmeasurable LD₅₀. Eighty SPF-grade KM mice (half male and half female) were randomly divided into the blank control group and treatment group, and a single intragastric administration was given within 24 hours. The treatment group was given 3.5 g/kg Huoxin pill liquid, while the control group was given the same volume of normal saline. After administration, the mice were observed for 14 consecutive days. The body weight, food intake and water consumption of mice were recorded before administration and 1, 3, 5, 8, and 14 days after administration. Ten males and females were chosen from each group at 1 d and 14 d after administration, and blood was drawn after removal of the eyeballs. The blood routine analysis was conducted and blood biochemical indicators were detected. The changes of dissected organs were observed, and the heart, liver, spleen, lung, and kidney were also dissected for histopathological examination. Results Within 3 hours of administration the mice showed symptoms of poisoning, including ataxia, malaise, prone convulsions and accelerated breathing. The second day, mice in the treated group returned to normal. The food intake of male mice in the treatment group was significantly lower than that in the control group at the first day after administration (P<0.05), but there was no significant change in the food intake of either group 3 days after administration. Compared with the control group, no significant change in body weight, water consumption, organ indexes, blood routine analysis, or blood biochemical indexes was observed in the treatment group (P>0.05). Histopathology showed inflammatory cell infiltration in the heart epicardium, inflammatory cell infiltration in the central vein of livers, and slight vacuolation of hepatocytes in the treatment group. Conclusion The maximum tolerance dose of mice is orally 3.5 g/kg, which is 1 750 times the daily dosage of a 60 kg adult, suggesting that Huoxin pills are orally safe.

Key words: Huoxin pills, acute toxicity, maximum tolerance test, mice, toxical target organs

CLC Number:

R994.1

MO Zunhui, CHEN Meixian, WANG Pengcheng, WANG Lingli, LIAO Yiqiu, LI Zehua. Acute Toxicity of Huoxin Pills in Mice[J]. Chinese Journal of Pharmacovigilance, 2021, 18(10): 924-929.

References

[1] Hu LJ, Ding SG, Jiao YC, et al.The observation on the resistive effect of the bufo’s electrocar-diograph’s changes by high k+ through Huoxinwan[J]. Journal of Hubei University (Nature Science)(湖北大学学报(自然科学版)), 1989, 11(2): 69-71, 76.
[2] Zhang XN, Li ZS, Wang JQ, et al.Effects of Huoxinwan on isolated working heart of guinea pig[J]. Traditional Chinese Drug Research and Clinical Pharmacology(中药新药与临床药理), 1998, 9(3): 163-165, 191.
[3] Zhang XN, Li ZS, Wang JQ, et al. Protective effects of huoxinwan on ischemic myocardium in anesthetized pigs[J]. Traditional Chinese Drug Research and Clinical Pharmacology(中药新药与临床药理), 1998, 9(4): 209-211, 251-252.
[4] Li ZS, Zhang XN, Wang JQ, et al. Effects of Huoxinwan on isolated myocardium of guinea pig and hemodynamics of anesthetized dog in vivo[J]. Traditional Chinese Drug Research and Clinical Pharmacology(中药新药与临床药理), 1999, 10(3): 149-152, 191-192.
[5] Liang XP, Guo CX, Ma J, et al.Treatment of stable pectoris of coronary heart disease patients by Huoxin Wan(concentrated pill): a multicenter, randomized, double-blinded, placebo-controlled clinical trial[J]. Chinese Journal of Integrated Traditional and Western Medicine(中国中西医结合杂志), 2018, 38(3): 289-294.
[6] Duan WH, Xu H, Wang CP, et al.A multicenter, randomized, double-blind, placebo-controlled clinical study of Huoxin Wan(concentrated pill) for the treatment of stable angina pectoris with the syndrome of qi deficiency and blood stasis[J]. Chinese Journal of Evidence-Based Cardiovascular Medicine(中国循证心血管医学杂志), 2016, 8(9): 1110-1115.
[7] Liu Z, Yan XG, Wang XG, et al.Clinical observation of Huoxin Capusle on angina pectoris of coronary heart disease[J]. Chinese Journal of Information on Traditional Chinese Medicine(中国中医药信息杂志), 2007, 14(6): 11-12.
[8] Dong ST, Yang J, Zhang XQ, et al.Experimental study on acute toxicity of Dendrobium Devonianum extract in mice[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2019, 16(5): 257-259.
[9] Chang RX, Cui YZ, Xu C, et al.Toxicology observation of LD50 and maxium tolerance of add and subtract Buzhong Yiqi Decoction to mice[J]. Heilongjiang Animal Science and Veterinary Medicine(黑龙江畜牧兽医), 2019(11): 127-131, 183.
[10] Chen Q.Research Methods in Pharmacology of Chinese Materia Medica(中药药理研究方法学)[M]. Beijing: People’s Medical Publis-hing House, 2011: 107-121.
[11] Xie XF, Peng C.Study progress of multidimensional evaluation and integrated analysis between toxicity and efficacy on heart of Radix Aconiti Lateralis Praeparata[J]. World Chinese Medicine(世界中医药), 2017, 12(11): 2555-2562.
[12] Wang NQ, Zhang L, Yang XY, et al.Toxic tranditional Chinese medicine of animal origin: historical perspective and modern studies[J]. Herald of Medicine(医药导报), 2019, 38(11): 1425-1430.
[13] Tan WY, Xia Y, Li YP, et al.Study on the effect of the toxic and active ingredients of aconite on the isolated frog heart and its related mechanism[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床), 2019, 35(3): 95-101.
[14] Peng JB, Tao Q, Li JH, et al.Acute and sub-chronic toxicity study of Chansu Pellets[J]. China Animal Husbandry & Veterinary Medicine(中国畜牧兽医), 2017, 44(5): 1508-1517.
[15] Sun J, Li H, Zhang GP, et al.Combination of ginseng, roasted liquorice and radix aconite chamichaeli and their effect on mice acute toxicity[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床), 2019, 35(2): 96-101.
[16] Zhou J, He RR, Jiang JJ, et al.Approaches to investigate the compatibility for reducing toxicity using a case of Bezoar and Toad Venom[J]. Journal of Nanjing University of Traditional Chinese Medicine(南京中医药大学学报), 2018, 34(4): 330-333.
[17] Quan ZY, Chen J, Li DK, et al.Hepatotoxicity of short time oral administration of aqueous extract of Polygoni Multflori Radix in rats[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2017, 14(6): 321-325.
[18] Chen JR, Liu X, Li DM, et al.Experimental study on acute toxicity of pinecone extracts from Pinus yunnanensis Fr.[J]. Lishizhen Medicine and Materia Medica Research(时珍国医国药), 2017, 28(8): 1837-1840.