Hydatid Cyst Killing Mechanism of Ziziphora tenuior by Inducing Apoptosis via Mitochondrial Intrinsic Pathway

Document Type: Original paper

Authors

1 Cellular & Molecular Research Institute, Qazvin University of Medical Sciences, Qazvin, Iran. Department of Parasitology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

2 Department of Immunology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

3 Cellular & Molecular Research Institute, Qazvin University of Medical Sciences, Qazvin, Iran.

4 Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.

5 Gorgan Congenital Malformations Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

6 Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

7 Department of Social Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Abstract

Background and objectives: Ziziphora tenuior is considered as an appropriate protoscolicidal agent yet the mechanism of such effect is not known so far. The aim of this study was to evaluate the apoptotic effect of Z. tenuior extract on protoscolices of hydatid cyst. Methods: Protoscolices were collected aseptically and the Bradford test was employed to determine the number required for the experiments. Various concentrations of Z. tenuior extract (5, 50, and 100 mg/mL) was incubated with hydatid cyst protoscolices at 37 oC and 5% Co2 for 4 h. The apoptotic effect of Z. tenuior extract on hydatid cyst protoscolices and the evaluation of caspases 3, 8, and 9 activities were ditermined using ELISA-based commercial diagnostic kits. Results: In the present study, 50 and 100 mg/mL of Z. tenuior extract produced apoptosis in the protoscolices of hydatid cyst significantly (p<0.05). Also, the activity of caspase 3 at 50 and 100 mg/mL significantly increased by 29.99% and 36.01%, respectively (p<0.05). Similarly, caspase 9 also demonstrated a significant increased activity up to 15.23%, and 45.31% at the same concentrations used for caspase 3, respectively (p<0.05). Conclusion: Our findings in this study indicated that, Z. tenuior extract can induce apoptotic cell death on hydatid cyst protoscolices by increasing the activity of caspases 3 and 9 via the internal apoptotic pathway.

Keywords

Main Subjects


[1] Adas G, Arikan S, Kemik O, Oner A, Sahip N, Karatepe O. Use of albendazole sulfoxide, albendazole sulfone, and combined solutions as scolicidal agents on hydatid cysts (in vitro study). World J Gastroenterol. 2009; 15(1): 112-116.

[2] Eckert J, Deplazes P. Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbiol Rev. 2004; 17(1): 107-135.

[3] Thompson RA, Mc Manus DP. Towards a taxonomic revision of the genus Echinococcus. Trends Parasitol. 2002; 18(10): 452-457.

[4] Rokni MB. Echinococcosis/hydatidosis in Iran. Iranian J Parasitol. 2009; 4(2): 1-16.

[5] Mandal S, Mandal MD. Human cystic echinococcosis: epidemiologic, zoonotic, clinical, diagnostic and therapeutic aspects. Asian Pac J Trop Med. 2012; 5(4): 253-260.

[6] Topcu O, Aydin C, Arici S, Duman M, Koyuncu A, Sen M. The effects of various scolicidal agents on the hepatopancreatic biliary system. Visceral Med. 2006; 22(3): 185-190.

[7] McManus DP, Zhang W, Li J, Bartley PB. Echinococcosis. Lancet. 2003; 362(9392): 1295-1304.

[8] Moazeni M, Nazer A. In vitro lethal effect of Zingiber officinale R. on protoscolices of hydatid cyst from sheep liver. Microbiol Res. 2011; 2(2): 91-94.

[9] Shahnazi M, Azadmehr A, Andalibian A, Hajiaghaee R, Saraei M, Alipour M. Protoscolicidal and immunomodulatory activity of Ziziphora tenuior extract and its fractions. Asian Pac J Trop Med. 2016; 9(11): 1062-1068.

[10] Shahnazi M, Azadmehr A, Latifi R, Hajiaghaee R, Saraei M, Alipour M. In vitro protoscolicidal effects of various concentrations of Ziziphora tenuior L. extract at different exposure times. Avicenna J Phytomed. 2016; 6(4): 376-382.

[11] Formigli L, Conti A, Lippi D. “Falling leaves": a survey of the history of apoptosis. Minerva Med. 2004; 95(2): 159-164.

[12] Kanan JH, Chain BM. Modulation of dendritic cell differentiation and cytokine secretion by the hydatid cyst fluid of Echinococcus granulosus. Immunology. 2006; 118(2): 271-278.

[13] Hu H, Kang J, Chen R, Mamuti W, Wu G, Yuan W. Drug-induced apoptosis of Echinococcus granulosus protoscoleces. Parasitol Res. 2011; 109(2): 453-459.

[14] Hashemi M, Ghavami S. Methods of studying the apoptosis. J Rafsanjan Uni Med Sci. 2008; 7(1): 71-78.

[15] Israels ED, Israels LG. The cell cycle. Oncologist. 2000; 5(6): 510-513.

[16] Hajiaghaee R, Monsef‐Esfahani HR, Khorramizadeh MR, Saadat F, Shahverdi AR, Attar F. Inhibitory effect of aerial parts of Scrophularia striata on matrix metalloproteinases expression. Phytother Res. 2007; 21(12): 1127-1129.

[17] Lötsch F, Naderer J, Skuhala T, Groger M, Auer H, Kaczirek K, Waneck F, Ramharter M. Intra-cystic concentrations of albendazole-sulphoxide in human cystic echinococcosis: a systematic review and analysis of individual patient data. Parasitol Res. 2016; 115(8): 2995-3001.

[18] Gavara CG, López-Andújar R, Ibáñez TB, Ángel JM, Herraiz ÁM, Castellanos FO, Ibars EP, Rodríguez FS. Review of the treatment of liver hydatid cysts. World J Gastroenterol. 2015; 21(1): 124-131.

[19] Tripathy S, Sasmal P, Rao PB, Mishra TS, Nayak S. Cetrimide-chlorhexidine-induced multiorgan failure in surgery of pulmonary hydatid cyst.Ann Card Anaesth. 2016; 19(3): 557-560.

[20] Shi H, Lei Y, Wang B, Wang Z, Xing G, Lv H, Jiang Y. Protoscolicidal effects of chenodeoxycholic acid on protoscoleces of Echinococcus granulosus. Exp Parasitol. 2016; 167: 76-82.

[21] Smyth JD, Barrett NJ. Procedures for testing the viability of human hydatid cysts following surgical removal, especially after chemotherapy. Trans R Soc Trop Med Hyg.1980; 74(5): 649-652.

[22] Paredes R, Jiménez V, Cabrera G, Iragüen D, Galanti N. Apoptosis as a possible mechanism of infertility in Echinococcus granulosus hydatid cysts.J Cell Biochem. 2007; 100(5): 1200-1209.

[23] De S, Pan D, Bera AK, Sreevatsava V, Bandyopadhyay S, Chaudhuri D, Kumar S, Rana T, Das S, Das SK, Suryanaryana VV, Singh MN, Bhattacharya D. In vitro assessment of praziquantel and a novel nanomaterial against protoscoleces of Echinococcus granulosus. J Helminthol.2012; 86(1): 26-29.

[24] Chachoyan AA, Oganesyan GB. Anti-tumor activity of some species of the family Lamiaceae. Rastit Resur. 1996; 32(4): 59-63.

[25] Amiri A, Tayarani-Najaran Z, Karimi G, Mousavi S. Evaluation of Lavandula angustifolia cytotoxic and apoptotic effects on human cervical cancer cell line (Hela) in compare with normal cells. Res Pharma Sci. 2012; 7(5): 141.

[26] Escobar FM, Cariddi LN, Sabini MC, Reinoso E, Sutil SB, Torres CV, Zanon SM, Sabini LI. Lack of cytotoxic and genotoxic effects of Minthostachys verticillata essential oil: studies in vitro and in vivo. Food Chem Toxicol. 2012; 50(9): 3062-3067.

[27] Banerjee PP, Bandyopadhyay A, Harsha SN, Policegoudra RS, Bhattacharya S, Karak N, Chattopadhyay A. Mentha arvensis (Linn.)-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells. Breast Cancer (Dove Med Press). 2017; 9: 265-278.

[28] Chauhan AK, Bahuguna A, Paul S, Kang SC. Thymol elicits HCT-116 colorectal carcinoma cell death through induction of oxidative stress. Anticancer Agents Med Chem. 2018; 17(14): 1942-1950.

[29] Li Y, Wen JM, Du CJ, Hu SM, Chen JX, Zhang SG, Zhang N, Gao F, Li SJ, Mao XW, Miyamoto H. Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis. Biochem Biophys Res Commun. 2017; 491(2): 530-536.

[30] Köhler C, Orrenius S, Zhivotovsky B. Evaluation of caspase activity in apoptotic cells. J Immunol Methods. 2002; 265(1-2): 97-110.

[31] Kang JF, Hu HH, Baishanbieke, Chen R, Abulizi. In vitro observation on the apoptosis induced by H2O2 in protoscolex of Echinococcus granulosus. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2008; 26(5): 332-337.

[32] Pensel PE, Maggiore MA, Gende LB, Eguaras MJ, Denegri MG, Elissondo MC. Efficacy of essential oils of Thymus vulgaris and Origanum vulgare on Echinococcus granulosus. Interdiscip Perspect Infect Dis. 2014; Article ID 693289.

[33] Amirghofran Z, Azadmehr A, Bahmani M, Javidnia K. Stimulatory effects of Euphorbia cheiradenia on cell mediated immunity and humoral antibody synthesis. Iran J Immunol. 2008; 5(2): 115-123.

[34] Amirghofran Z, Azadmehr A, Javidnia K. Haussknechtia elymatica: a plant with immunomodulatory effects. Iran J Immunol.2007; 4(1): 26-31

[35] Valiyari S, Baradaran B, Abdolalizadeh J, Bandehagh A, Azadmehr A, Hajiaghaee R. Inhibitory and cytotoxic activities of Salvia officinalis L. extract on human lymphoma and leukemia cells by induction of apoptosis. Adv Pharm Bull.2013; 3(1): 51-55.

[36] Amirghofran Z, Bahmani M, Azadmehr A, Ashouri E, Javidnia K. Antitumor activity and apoptosis induction in human cancer cell lines by Dionysia termeana. Cancer Invest.2007; 25(7): 550-554.

[37] Shahnazi M, Azadmehr A, Jondabeh MD, Hajiaghaee R, Norian R, Aghaei H, Saraei M, Alipour M. Evaluating the effect of Myrtus communis on programmed cell death in hydatid cyst protoscolices. Asian Pac J Trop Med. 2017; 10(11): 1072-1076.

[38] Shahnazi M, Azadmehr A, Hajiaghaee R, Mosalla S, Latifi R. Effects of Artemisia absinthium L. Extract on the maturation and function of dendritic cells. Jundishapur J Nat Pharm Prod. 2015; 10(2): 1-6.