Evaluation of Artesunate and Praziquantel Combination Ther-apy in Murine Schistosomiasis mansoni
AbstractBackground: Despite the global efforts to control schistosomiasis, still prevalence in endemic regions unchanged. The present study was conducted to investigate the possible role of artesunate (AS) and praziquantel (PZQ) combination in enhancing cure in pre-patent and patent Schistosoma mansoni infection, and study the role of apoptosis in evaluation of the drugs efficacy.Methods: Eighty laboratory-bred Swiss albino male mice were classified into four groups (20 mice each); control, PZQ treated (500 mg/kg), AS treated (400 mg/kg) and combined AS (400 mg/kg) + PZQ (500 mg/g) groups. Efficacy of the drugs was assessed by parasitological (egg count/gram stool, worm burden, tissue egg load, oogram pattern), histopathological (haematoxylin and eosin –for detection of type of hepatic granulomas, number & diameter) and immunohistochemical studies (P53 and Bcl-2 markers for determination of inflammatory cells and the degree of apoptosis).Results: Significant reduction was recorded in stool egg count, tissue egg count (liver and intestine), worm burden, granuloma number and size and changed oogram patterns in artesunate -praziquantel combined group followed by artesunate monotherapy group. There was a significant increase in the apoptotic proteins P53 and slight increase in anti-apoptotic proteins Bcl-2 in the infected group compared to the control healthy group. A significant decrease and increase in P53 & Bcl-2 expressions respectively were observed in artesunate – praziquantel combined group compared to control infected group.Conclusion: artesunate-praziquantel combination is a potential upcoming chemotherapy for schistosomiasis mansoni. Both Bcl-2 and P53 are good markers assessing S. mansoni apoptosis, morbidity and chemotherapy efficacy.
World Health Organization. Schistosomiasis. http://www.who.int/en/news-room/fact-sheets/detail/schistosomiasis
Thétiot-Laurent SA, Boissier J, Robert A, Meunier B. Schistosomiasis chemotherapy. Angew Chem Int Ed Engl. 2013; 52(31):7936-56.
Wang W, Wang L, Liang YS. Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitol Res. 2012; 111(5):1871-7.
Doenhoff MJ, Cioli D, Utzinger J. Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis. 2008; 21(6):659-67.
Lee EF, Young ND, Lim NT, Gasser RB, Fairlie WD. Apoptosis in schistosomes: toward novel targets for the treatment of schistosomiasis. Trends Parasitol. 2014;30(2):75-84.
Corrêa Soares JB, Menezes D, Vannier-Santos MA et al. Interference with haemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLoS Negl Trop Dis. 2009; 3(7):e477.
Inyang-Etoh PC, Ejezie GC, Useh MF, Inyang-Etoh EC. Efficacy of artesunate in the treatment of urinary schistosomiasis, in an endemic community in Nigeria. Ann Trop Med Parasitol. 2004; (98): 491–499.
Abdin AA, Ashour DS, Shoheib ZS. Artesunate effect on schistosome Thioredoxin Glutathione Reductase and Cytochrome c Peroxidase as new molecular targets in Schistosoma mansoni-infected mice. Biomed Environ Sci. 2013 Dec;26(12):953-61.
Bechmann LP, Marquitan G, Jochum C et al. Intoxication compared with acute-on-chronic liver failure. Liver Int. 2008; 28(5): 713–716.
Collavin L, Lunardi A, Del Sal G. p53-family proteins and their regulators: hubs and spokes in tumor suppression. Cell Death Differ. 2010; 17(6):901-11.
de la Coste A, Fabre M, McDonell N et al. Differential protective effects of Bcl-xL and Bcl-2 on apoptotic liver injury in transgenic mice. Am J Physiol. 1999; 277(3 Pt 1):G702-8.
Tousson E, Beltagy DM, Gazia MA, Al-Behbehani B. Expressions of P53 and CD68 in mouse liver with Schistosoma mansoni infection and the protective role of silymarin. Toxicol Ind Health. 2013; 29(8):761-70.
Botros SS, Hammam O, Mahmoud M, Bergquist R. Praziquantel efficacy in mice infected with PZQ non-susceptible S. mansoni isolate treated with artemether: parasitological, biochemical and immunohistochemical assessment. APMIS. 2010; 118(9):692-702.
Peters AP, Warren KS. A rapid method of infecting mice and other laboratory animals with Schistosoma mansoni subcutaneous injection. J Parsitol. 1969; 55: 558- 563.
Jiraungkoorskul W, Sahaphong S, Sobhon P, Riengrojpitak S, Kangwanrangsan N. Effects of praziquantel and artesunate on the tegument of adult Schistosoma mekongi harboured in mice. Parasitol Int. 2005; 54(3):177-83.
Khyyal MT. Significance of worm shifts in experimental S. mansoni, with emphyasis on the action of the anesthetics. Nature. 1965; 205: 1331-1332.
Katz N, Chaves A, Pellegrino J. A simple device for quantitative stool thick smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo.1972; 14(6):397-400.
Duvall RH, DeWitt WB. Technique for recovering adult schistosomes from laboratory animals. Am J Trop Med Hyg. 1967; 16: 438-486.
Cheever AW. Postmortem study of schistosomiasis manosni in man. Am J Trop Med Hyg. 1968; 17: 38-64.
Tendler M, Pinto RM, Oliveira Lima A, Gebara G, Katz N. Schistosoma mansoni: vaccination with adult worm antigens. Int J Parasitol. 1986; 16(4):347-52.
Pellegrino J, Oliveira Ca, Faria J, Cunha As. New approach to the screening of drugs in experimental schistosomiasis mansoni in mice. Am J Trop Med Hyg. 1962; 11:201-15.
von Lichtenberg. Host response to eggs of Schistosoma mansoni. I Granuloma formation in the sensitized laboratory mouse. Am J Pathol. 1962; 41:711-31.
Hsu SM, Raine L. Protein A, Avidin and biotin in immunohistochemistry. J Histochem Cytochem. 1981; 29(11):1349-53.
Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin induced lung injury and ameliorating role of L carnitine. Biomed Pharmacother. 2014; 68(5):631-9.
El-Beshbishi SN, Taman A, El-Malky M et al. First insight into the effect of single oral dose therapy with artemisinin–naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection. Int J Parasitol. 2013; 43(7):521-30.
Xiao SH, You JQ, Yang YQ, Wang CZ. Experimental studies on early treatment of schistosomal infection with artemether. Southeast Asian J Trop Med Public Health. 1995; 26(2):306-18.
Araújo N, Kohn A, Katz N. Therapeutic evaluation of artesunate in experimental Schistosoma mansoni infection. Rev Soc Bras Med Trop. 1999; 32(1):7-12.
Botros SS, Mahmoud MR, Moussa MM, Nosseir MM. Immuno histopathological and biochemical changes in Schistosoma mansoni-infected mice treated with artemether. J Infect. 2007; 55(5):470-7.
Fallon PG, Sturrock RF, Niang AC, Doenhoff MJ. Diminished susceptibility to praziquantel in a Senegal isolate of Schistosoma mansoni. Am J Trop Med Hyg. 1995; 53(1):61-2.
Aragon AD, Imani RA, Blackburn VR et al. Towards an understanding of the mechanism of action of praziquantel. Mol Biochem Parasitol. 2009; 164(1):57-65.
Shuhua X, Jiqing Y, Jinying M et al. Effect of praziquantel together with artemether on Schistosoma japonicum parasites of different ages in rabbits. Parasitol Int. 2000; 49(1):25-30.
Elmorshedy H, Tanner M, Bergquist RN et al. Prophylactic effect of artemether on human schistosomiasis mansoni among Egyptian children: A randomized controlled trial. Acta Trop. 2016; 158:52-58.
Abdel-Fattah NS, Ahmed SN. Evaluation of mefloquine-praziquantel combination therapy in prepatent and patent Schistosoma mansoni infection in mice. Sci Parasitol. 2011; 12(3):139-149.
Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell. 2011; 147(4):742-58.
Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ. Bcl2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A. 1991; 88(16):6961-5.
Sandra D. Melman, Michelle L. Steinauer, Charles Cunningham et al. Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni. PLoS Negl Trop Dis. 2009; 3(8): e504.
McCreesh N, Nikulin G, Mark BM. predicting the effects of climate change On Schistosoma mansoni transmission in eastern Africa. Parasit Vectors. 2015; 8:4-10.