Search In this Thesis
   Search In this Thesis  
العنوان
In Vitro Parasitological, Biochemical, Molecular and
Ultrastructure Studies of the Effect of the Thioredoxin
Reductase Inhibitor (Auranofin) on Adult Fasciola spp. /
المؤلف
AbouGalalah, Doaa Ibrahim Mostafa.
هيئة الاعداد
باحث / دعاء إبراهيم مصطفى أبوجلاله
مشرف / نشأت السيد ناصف
مشرف / أميمه كامل الشافعى
مناقش / نانسي محمود حربة
مناقش / محمود عبدالنبي الصيفي
الموضوع
Parasitologys.
تاريخ النشر
2021.
عدد الصفحات
143 P. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأحياء الدقيقة (الطبية)
تاريخ الإجازة
2/1/2022
مكان الإجازة
جامعة المنوفية - كلية الطب - الطفيليات الطبية
الفهرس
Only 14 pages are availabe for public view

from 165

from 165

Abstract

Fascioliasis is a food-borne parasitic disease caused by Fasciola spp. (species);
Fasciola hepatica (F. hepatica) and Fasciola gigantica (F. gigantica). The disease is an
important zoonosis that can infect humans as incidental hosts. The available treatment for
fascioliasis is triclabendazole (TCBZ) which is a benzimidazole derivative with
antihelminthic activity and it is known to be highly effective against F. hepatica and F.
gigantica. However, over-reliance on this drug in the treatment of human fascioliasis
(HF) and animal fascioliasis (AF) has led to the development of resistance. This emerging
resistance necessitates identification of novel and alternative therapeutic measures.
The aim of the present study was to evaluate the effect of Thioredoxin reductase
inhibitor (auranofin) on adult Fasciola spp. in vitro through a series of parasitological,
biochemical, molecular and ultrastructure studies.
This study was designed using 75 adult Fasciola worms of nearly equal size to
study the antihelminthic effects of auranofin against adult Fasciola worms. Five groups
were included (each group included 15 F. gigantica adult worms). GI: adult worms were
incubated in RPMI-1640 medium and served as a normal control group (NC), GII: worms
were incubated in RPMI-1640 medium containing TCBZ at a concentration of 20 μL/mL
and served as the TCBZ- exposed group, GIII: worms were incubated in RPMI-1640
medium containing auranofin at a concentration of 3 μg/mL were served as the auranofinexposed
group a, GIV: worms were incubated in RPMI-1640 medium containing
auranofin at a concentration of 5μg/mL and served as the auranofin- exposed group b and
GV: worms were incubated in RPMI-1640 medium containing auranofin at a
concentration of 10 μg/mL and served as the auranofin- exposed group c.
The five groups were incubated for 3 hours at room temperature in an atmosphere
of 5 % CO2 and then were subjected to motility assay, egg hatching, scanning &
transmission electron microscope, histopathological, immunohistochemical studies for
evaluation of the expression of caspase-3, assay of GST, analysis of SOD activity and
real- time PCR for cathepsin-L gene expression.
On assessment of worm motility changes among the studied groups, no major loss
of activity in the control worms was observed. The decrease in the motility of worms
exposed to auranofin was both time and concentration dependent. The highest
concentration (10 μg/ml) of the auranofin produced inhibition of the motility of worms as
compared to the normal control and TCBZ- exposed group. After three hours, all worms in
auranofin- exposed three groups (a, b & c) were dead (score 0). In normal control group
(GⅠ) and TCBZ- exposed group, only 3 and 5 worms respectively were dead (score 0)
(Table 1). Also, decrease in motility of worms was significant in relation to time in
auranofin- exposed groups (GⅢ, GⅣ and GⅤ) (P<0.001) (Table 8).
Results of egg hatching in the studied groups showed that in both control (GⅠ) and
TCBZ- exposed group (GⅡ), there was normal immature yellowish brown operculated
eggs with thin shell and normal egg hatching. In auranofin- exposed groups (GⅢ, GⅣ
and GⅤ), there was decrease in egg hatching with damage, disintegration, shrinking and
collapse of egg. Also, there was significant decrease in hatching of F. gigantica eggs in
normal control group (GⅠ) with increase in duration of incubation (P: 0.001), TCBZexposed
(GⅡ) (P: 0.003), auranofin- exposed a (GⅢ) (P: 0.041), auranofin- exposed b
(GⅣ) (P: 0.013) and auranofin- exposed c (GⅤ) with percentage of 40%, 13.3%, 13.3%