Experimental study on the treatment of secondary Alveolar echinococcosis with thiacloprid
LIU Chuan-chuan1,2,3, MA Lan3, GE Ri-li2,3, FAN Hai-ning1,2
1.Affiliated Hospital of Qinghai University, Xining 810001, China; 2. The Key Laboratory of Hydatidosis Research in Qinghai Province, Xining 810001, China; 3. Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining 810001, China
Abstract:The aim of this study was to observe the killing effects of different concentrations of thiacloprid (Thia) on echinococcosis, and to evaluate the effects of thiacloprid in the treatment of Echinococcus multilocularis, with a view to explore the potential of thiacloprid as a lead compound against echinococcosis. In in vitro experiments, different concentrations of Thia were applied to the protoscolices of E. multilocularis. The survival of the protoscolices was evaluated with 0.1% eosin staining. The ultrastructural changes in the protoscolices were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In in vivo experiments, mice with secondary E. multilocularis infection were divided into three groups: a model group, albendazole group (ABZ, 100 mg/kg) and Thia group (20 mg/kg). Mice without infection were used as the control group. After 4 weeks of intragastric administration, the spleens and hydatid cysts were isolated and weighed, the spleen index and cyst suppression rate were calculated, and the morphological changes of cysts were observed after HE staining. In addition, thiacloprid toxicity was evaluated in vitro (LO2 and HepG2 cells) and in vivo (Balb/c mice). In vitro, 40 μg/mL thiacloprid showed a killing effect on the protoscolices and caused the destruction of the surface and internal structure of the protoscolices. After 4 weeks of in vivo drug therapy, the spleen index of the mice was higher than that in the model group (P<0.05), and the weight of hydatid cysts was lower than that in the model group (P<0.05). The histopathology of the hydatid cysts showed no germinal layer in the Thia group. There was no significant cytotoxicity when the concentration of thiacloprid was lower than 80 μg/mL, and there was no significant in vivo hepatorenal toxicity when the concentration of thiacloprid was 20 mg/kg. Thiacloprid exhibits a clear anti-E. multilocularis effect in vivo and in vitro, can enhance immune function in mice, and may have the potential to be developed as a lead compound against echinococcosis.
刘川川, 马兰, 格日力, 樊海宁. 噻虫啉治疗继发性泡型包虫病的实验研究[J]. 中国人兽共患病学报, 2020, 36(12): 1006-1013.
LIU Chuan-chuan, MA Lan, GE Ri-li, FAN Hai-ning. Experimental study on the treatment of secondary Alveolar echinococcosis with thiacloprid. Chinese Journal of Zoonoses, 2020, 36(12): 1006-1013.
[1] Spahn S, Helmchen B, Zingg U.Alveolar echinococcosis of the right adrenal gland: a case report and review of the literature[J]. J Med Case Rep, 2016, 10(1): 325. DOI: 10.1186/s13256-016-1115-0 [2] Atalan G, Sivrioglu AK, Sönmez G, et al.A Case of Alveolar Echinococcosis Presenting as Cerebral and Spinal Intradural Metastases[J]. Eurasian J Med, 2016, 48(2): 149-152. DOI: 10.5152/eurasianjmed.2015.15003 [3] Sade R, Kantarci M, Ogul H, et al. Differentiation between hepatic alveolar echinococcosis and primary hepatic malignancy with diffusion-weighted magnetic resonance imaging[J]. Diagn Interv Imaging, 2017,S2211-5684(17):30240-30241. DOI: 10.1016/j.diii.2017.09.007 [4] Xu Wang, Jiayu Liu, Qingqiu Zuo, et al.Echinococcus Multilocularis and Echinococcus Shiquicus in a small mammal community on the Eastern Tibetan Plateau: host species composition, molecular prevalence, and epidemiological implications[J]. Parasit Vectors, 2018, 11(1): 302. DOI: 10.1186/s13071-018-2873-x [5] Yangdan Cairang, Lingqiang Zhang, Bin Ren, et al.Efficacy and safety of ultrasound-guided percutaneous microwave ablation for the treatment of hepatic alveolar echinococcosis: a preliminary study[J]. Medicine (Baltimore), 2017, 96(27): e7137. DOI: 10.1097/MD.0000000000007137 [6] Graeter T, Ehing F, Oeztuerk S,et al.Hepatobiliary complications of alveolar echinococcosis: a long-term follow-up study[J]. World J Gastroenterol, 2015, 21(16): 4925-4932. DOI: 10.3748/wjg.v21.i16.4925 [7] Pohnan R, Ryska M, Hytych V, et al.Echinococcosis mimicking liver malignancy: a case report[J]. Int J Surg Case Rep, 2017, 36(C): 55-58. DOI: 10.1016/j.ijscr.2017.04.032 [8] Du C, Liu Z, Yang X, et al.Hepatectomy for patients with alveolar echinococcosis: long-term follow-up observations of 144 cases[J]. Int J Surg, 2016, 35: 147-152. DOI: 10.1016/j.ijsu.2016.09.094 [9] Tomizawa M, Casida JE.Molecular recognition of neonicotinoid insecticides: the determinants of life or death[J]. Acc Chem Res, 2009, 42(2): 260-269. DOI: 10.1021/ar800131p [10] Phua DH, Lin CC, Wu ML, et al.Neonicotinoid insecticides: an emerging cause of acute pesticide poisoning[J]. Clin Toxicol (Phila), 2009, 47(4): 336-341. DOI: 10.1080/15563650802644533 [11] Faro LRF, Oliveira IM, Durán, R, et al.In vivo neurochemical characterization of clothianidin induced striatal dopamine release[J]. Toxicology,2012, 302(2/3): 197-202. DOI: 10.1016/j.tox.2012.07.017 [12] Tomizawa M, Casida JE.Selective Toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptors[J]. Annu Rev Entomol, 2003, 48(1): 339-364. DOI: 10.1146/annurev.ento.48.091801.112731 [13] Quan Zhang, Ximing Wang, Zhe Li, et al.Simultaneous determination of nine neonicotinoids in human urine using isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry[J]. Environ Pollut, 2018, 240: 647-652. DOI: 10.1016/j.envpol.2018.04.144 [14] Calderón-Segura ME, Gómez-Arroyo S, Villalobos-Pietrini R, et al.Evaluation of genotoxic and cytotoxic effects in human peripheral blond lymphocytes exposed in vitro to neonicotinoid insecticides news[J]. J Toxicol, 2012, 2012:e612647. DOI: 10.1155/2012/612647 [15] 刘川川, 樊海宁, 马兰,等. 棘球绦虫和其它寄生性绦虫乙酰胆碱酯酶和烟碱型乙酰胆碱受体作为潜在药物靶点的研究进展[J]. 中国人兽共患病学报, 2019, 35(12):1122-1129. DOI: 10.3969/j.issn.1002-2694. 2019.00.157 [16] Shi Y, Wan X, Wang Z, et al.First description of Echinococcus ortleppi infection in China[J]. Parasit Vectors, 2019, 12(1): 398. DOI: 10.1186/s13071-019-3653-y [17] Yavor Asenov, Melih Akin, Cem Ibis, et al.Observed or predicted albendazole hepatotoxicity as an indication for a resection procedure in hepatic hydatid disease-a short series of cases[J]. Chirurgia (Bucur), 2019, 114(4): 522-527. DOI: 10.21614/chirurgia.114.4.524 [18] Gabriela V Ullio Gamboa, Patricia E Pensel, María C Elissondo, et al. Albendazole-lipid nanocapsules: optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus Granulosus[J]. Exp Parasitol, 2019, 198: 79-86. DOI: 10.1016/j.exppara.2019.02.002 [19] Negin Torabi, Faramarz Dobakhti, Soghrat Faghihzadeh, et al.In vitro and in vivo effects of chitosan-praziquantel and chitosan-albendazole nanoparticles on Echinococcus Granulosus Metacestodes[J]. Parasitol Res, 2018, 117(7): 2015-2023. DOI: 10.1007/s00436-018-5849-z [20] Cheng HS, Lee JXT, Wahli W, et al.Exploiting vulnerabilities of cancer by targeting nuclear receptors of stromal cells in tumor microenvironment[J]. Mol cancer, 2019, 18(1): 51. DOI: 10.1186/s12943-019-0971-9 [21] Díaz á, Sagasti C, Casaravilla C.Granulomatous responses in larval taeniid infections[J]. Parasite Immunol, 2018, 40(5): e12523. DOI: 10.1111/pim.12523 [22] Ito T, Connett JM, Kunkel SL, et al.The linkage of innate and adaptive immune response during granulomatous development[J]. Front Immunol, 2013,4:10. DOI: 10.3389/fimmu.2013.00010 [23] Almadani N, Almutairi B, Alassiri AH.Primary subcutaneous hydatid cyst with palisading granulomatous reaction[J]. Case Rep Pathol, 2013,2013:e126541. DOI: 10.1155/2013/126541 [24] Shahla Rostami-Rad, Rasool Jafari, Hossein Yousofi Darani.Th1/Th2-type cytokine profile in C57 black mice inoculated with live Echinococcus Granulosus protoscolices[J]. J Infect Public Health, 2018, 11(6): 834-839. DOI: 10.1016/j.jiph.2018.06.007 [25] Quagliariello V, Rossetti S, Cavaliere C, et al.Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences[J]. Oncotarget, 2017, 8(18): 30606-30616. DOI: 10.18632/oncotarget.16725