Dose-response relationship in Schistosoma mansoni juvenile and adult stages following limonin treatment in experimentally infected mice

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Eraky M.A.; El-Kholy A.A.E.-M.; Rashed G.A.E.-R.; Hammam O.A.; Moharam A.F.; Abou-Ouf E.A.-R.; Aly N.S.M.; Kishik S.M.; Abdallah K.F.; Hamdan D.I.

Journal: Parasitology Research

Publisher: Springer Verlag

Publication Date: 20 June 2016

Volume / Issue: Volume 115 / Issue 10

Pages: 4045–4054

ISSN: 9320113

DOI: 10.1007/s00436-016-5177-0

Scopus: View on Scopus

PubMed: 27325399

Document Type: Article

Authors and Affiliations

Eraky M.A., Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt; El-Kholy A.A.E.-M., Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt; Rashed G.A.E.-R., Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt; Hammam O.A., Department of Pathology, Theodore Bilharz Research Institute, Giza, Egypt; Moharam A.F., Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt; Abou-Ouf E.A.-R., Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt; Aly N.S.M., Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt; Kishik S.M., Department of Parasitology, Faculty of Medicine, Benha University, Benha, 13518, Egypt; Abdallah K.F., Medical Parasitology Department, College of Medicine, Taif University, Taif, Saudi Arabia; Hamdan D.I., Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

Abstract

Preventive chemotherapy with praziquantel is the mainstay of schistosomiasis control. However, drug resistance is an imminent threat, particularly with large-scale administration of praziquantel, in addition to much less efficacy against young schistosomes. Several biological activities of limonin have been explored such as insecticidal, insect antifeedant, and growth-regulating activity on insects as well as antimalarial, antiviral, anticancer, cholesterol-lowering, and antioxidant activities. This study investigates limonin as an alternative antischistosomal compound using two novel, single, oral dose regimens. In the current work, the therapeutic efficacy of different limonin dosing protocols was evaluated in experimentally infected mice harboring Schistosoma mansoni (Egyptian strain) juvenile or adult stages. Oral administration of limonin in a single dose of 50 or 100 mg/kg on day 21 post-infection (p.i.) resulted in a significant worm burden reduction of 70.0 and 83.33 %, respectively. The same dose given on day 56 p.i. reduced total worm burdens by 41.09 and 60.27 %, respectively. In addition, significant reductions of 34.90 and 47.16 % in the hepatic and 46.67 and 56.1 % in the intestinal tissue egg loads, respectively, associated with significant alterations in the oogram pattern with elevated dead egg levels. Limonin produced ameliorations of hepatic pathology with reduction in dimensions and number of granulomas. Limonin also produced a variety of tegumental alterations in treated worms including tubercular disruption, edema, blebbing, and ulcerations. Results obtained by this work elucidated promising limonin bioactivity against S. mansoni juvenile and adult stages and provided a basis for subsequent experimental and clinical trials. © 2016, Springer-Verlag Berlin Heidelberg.

Keywords

Adult; In vivo; Juvenile; Limonin; Natural plants; S. mansoni; Administration, Oral; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance; Female; Granuloma; Intestines; Limonins; Liver; Male; Mice; Parasite Egg Count; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Schistosomicides; antischistosomal agent; limonoid; animal experiment; animal model; animal tissue; antiparasitic therapy; Article; clinical assessment; clinical evaluation; clinical protocol; controlled study; dose response; drug efficacy; edema; egg parasitoid; helminthiasis; integumentary system; intestinal tissue; juvenile animal; liver granuloma; liver parenchyma; mouse; nematode life cycle stage; nonhuman; priority journal; scanning electron microscopy; single drug dose; therapy effect; ulcer; animal; disease model; drug effects; intestine; oral drug administration; parasite identification; parasitology; pathology

Citation Information

Scopus Citations: 12

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