Effect of Nitazoxanide, Artesunate Loaded Polymeric Nano Fiber and Their Combination on Experimental Cryptosporidi-osis

  • Enas Fakhry ABDELHAMED Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Sharkia Governorate, Egypt
  • Eman Magdy FAWZY Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Sharkia Governorate, Egypt
  • Said Mahmoud AHMED Department of Zoology, Faculty of Science, Zagazig University, Sharkia Governorate, Egypt
  • Rabab Sayed ZALAT Department of Medical Parasitology, Theodor Bilharz Research Institute, Giza, Egypt
  • Hayam Elsaid RASHED Department of Pathology, Faculty of Medicine, Zagazig University, Sharkia Governorate, Egypt
Keywords: Cryptosporidium, Oxidative stress, Artesunate, Polymeric nanofiber

Abstract

Background Cryptosporidium parvum  is a dangerous intestinal pathogen due to its  devastating  effect in immunocompromised individuals. Considering low efficacy, high toxicity in addition to the development of resistance for the drugs used, this study aimed to find a new alternative treatment having the advantage of lower doses and minimal toxicity. As complementary for our previous research, we used a novel combination between artesunate loaded polymeric nanofiber and nanozoxide that had not been tried yet. Methods Our experiment was performed on 60 immunocompromised mice that divided into six groups of 10 mice each: G I: infected control, G II: infected and treated with nanozoxide, G III: infected and treated with combination of artesunate, G IV: infected and treated with combination of nanozoxide and artesunate loaded nanofiber, G V: infected and treated with artesunate-loaded nanofiber, Group VI: uninfected control. Group IV had the highest oocyst reduction rate. Results The novel combination between artesunate loaded polymeric nanofiber and nanozoxide  has a harmonizing effect in reducing oocyst shedding, increasing total antioxidants activity, decreasing oxidative stress in tissues in addition to the marked improvement of histopathological features. Conclusions This combination has a promising therapeutic effect against cryptosporidiosis particularly in immunocompromised individuals considering minor toxicity.

References

Checkley W,White AC, Jaganath D, Arrowood MJ , Chalmers RM, Chen XM, et al. A review of the global burden, novel diagnostics, therapeutics and vaccine targets for Cryptosporidium.Lancet Infect Dis 2015;15:85–94.

Smith HV, Cacciò SM, Cook NR,Nichols AB, Tait A. Cryptosporidium and Giardia as foodborne zoonoses.Vet Parasitol 2007;149: 29-40.

Hunter PR, Nichols G. Epidemiology and clinical features of Cryptosporidium infection in immunocompromised patients. Clinic. Microbiol Rev 2002;15:145–154.

Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Sow SO, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prfospective, case-control study. Lancet 2013;13:209–222.

Rossignol JF. Cryptosporidium and Giardia: treatment options and prospects for new drugs. Exp Parasitol 2010;124:45–53.

Andrews KT, Fisher G, Skinner-Adams TS. Drug repurposing and human parasitic protozoan Diseases. Int J Parasitol. Drugs Drug Resist 2014;10:95–111.

Gargala G. Drug treatment and novel drug target against Cryptosporidium.Parasite 2008;15:275-281.

Manjunatha UH, Alexander TC, Leong FJ, Thierry T.Cryptosporidiosis drug discovery: opportunities and challenges, ACS. Infect Dis 2016;8:530–537.

Ferreira JF, Gonzalez JM. Analysis of underivatized artemisinin and related sesquiterpene lactones by high-performance liquid chromatography with ultraviolet detection, Phytochem Anal 2009;20:91–97.

Valderrábano J, Calvete C, Uriarte J. Effect of feeding bioactive forages on infection and subsequent development of haemonchus contortus in lamb faeces. Vet Parasitol 2010;172:89–94.

Ferreira JF, Laughlin JC, Delabays N, Magalhães PM.Cultivation and genetics of Artemisia annua for increased production of the anti-malarial artemisinin. Plant Genet Resour 2005;3: 206– 229

Morie A, Garg T , Goyal AK, Rath G . Nanofibers as novel drug carrier. J Artificial cells, nanomedicine and biotechnology 2014;44:135-143.

Garg T, Rath G, Goyal AK. Biomaterials-based nanofiber scaffold: targeted and controlled carrier for cell and drug delivery. J Drug Targeting 2015;23: 202-221.

Shenoy SL, Bates WD, Frisch HL, Wnek GE.Role of chain entanglements on fiber formation during electrospinning of polymer solutions: Good solvent, non-specific polymer– polymer interaction limit, Polymer 2005;46 :3372–3384.

Hibbs J B.Infection and Nitric Oxide. J Infect Dis 2002;185:S9-S17.

Ujjwal k, Mukherjee R, Nandi S, Bhushan B, Dimri U,Verma A.Disturbance of oxidant/antioxidant balance, acute phase response and high mobility group box-1 protein in acute undifferentiated diarrhea in cross bred piglets. Indian J. Anim.Sci. 2014;84 : 860-863.

Akaike T, Suga M, Maeda H.Free radicals in viral pathogenesis: molecular mechanisms involving superoxide and NO. Proc.Soc. Exp Biol Med 1998;217:64-73.

Waldman E, Tzipori S, Forsyth J. Separation of Cryptosporidium species oocysts from feces by using a percoll discontinuous density gradient. J. Clin. Microbiol. 1986;23:199-200.

Henriksen S, Pohlenz J. Staining of cryptosporida by a modified Ziehl-Neelsen technique. Acta Vet Scand 1981; 22(3–4): 594-596.

Suresh P, Rehg JE. Comparative evaluation of several techniques for purification of Cryptosporidium parvum oocysts from rat feces.Journal of Clinical Microbiology 1996 34: 38-40.

Tamer U, Flemming B. Electrospinning of cyclodextrin functionalized polyethylene oxide (PEO) Nanofibers J European Polymer 2009;45:1032–1037.

Rasmussen KR, Healey MC.Dehydroepiandrosterone - indeuced reduction of cryptosporidium parvum infection in aged Syrian golden hamster. J Parasitol 1992;78:554-557.

Benamrouz S, Guyot K, Gazzola S, Mouray A, Chassat T, Delaire B, Chabé M, Gosset P, Viscogliosi E, Dei-Cas E, Creusy C, Conseil V, Certad G.Cryptosporidium parvum infection in SCID mice infected with only one oocyst: qPCR assessment of parasite replication in tissues and development of digestive cancer. PLOS ONE 2012;7: e51232.

Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V.Method for the measurement of antioxidant activity in human fluids. J Clinical Pathology 2001;54:356–361.

Brennan PA, Conroy B,.Spedding AV. Expression of inducible nitric oxide synthase and p53 in oral epithelial dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2014;90:624–9.

Farthing MJ.Treatment options for the eradication of intestinal protozoa. Nat Clin Pract Gastrenterol. Hepatol 2006;3:436–45.

Chong LH, Lim M, Sultana N. Fabrication and Evaluation of Polycaprolactone/Gelatin-Based Electrospun Nanofibers with Antibacterial Properties.J Nanomaterials 2015:1-8.

Shaimaa AM, Noor AA, Ibrahim AA. The effect of aqueous alcohol Artemisia herba-alba and Thymus vulgaris extract on the Cryptosporidium parvum in theWhite Mouse (BALB/C). International J Advanced Research 2015;3: 31-35.

Wu L1, Jiang XG, Shen YJ, Lu ZX, Tu GH, Fu XL, Chen SX, Cao JP. Efficacy of Ginkgolic acids against Cryptosporidium andersoni in cell culture. Parasitol Res 2011;109:1475-9.

Abd-Ella O.H. Diagnosis and treatment of cryptosporidiosis: an update review. J Egypt Soc Parasitol 2014;44:455-66.

Ghiselli A, Serafini M , Natella F, Scaccini C.Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Bio-Assays for Oxidative Stress Status 2001:219–227.

Bhagat M, Sood S, Yadav A, Verma P, Manzoor N, Chakraborty D, Katoch R, Sangha N. Alterations in oxidative stress parameters and its associated correlation with clinical disease on experimental Cryptosporidium parvum infection in Swiss albino mice. J Parasit Dis 2017;41:707-712.

Kim MH, Seo JY, Liu KH, Kim JS.Protective effect of Artemisia annua L. extract against galactose-induced oxidative stress in mice. PLoS One 2014;9:e101486.

Published
2019-06-19
How to Cite
1.
ABDELHAMED EF, FAWZY EM, AHMED SM, ZALAT RS, RASHED HE. Effect of Nitazoxanide, Artesunate Loaded Polymeric Nano Fiber and Their Combination on Experimental Cryptosporidi-osis. Iran J Parasitol. 14(2):240-249.
Section
Original Article(s)