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العنوان
Study on MicroRNA-155,Butyrylcholinesterase and Adenosine Deaminase Activities in Mice Livers Infected with Strains of Toxoplasma gondii /
المؤلف
Abdel Aziz, Rawda Mahmoud Mohamed.
هيئة الاعداد
باحث / روضة محمود محمد عبدالعزيز
مشرف / منى محمد رشاد
مشرف / منى حسن الصياد
مشرف / نيفين عبدالمنعم حسين
مشرف / محمد عبدالرحمن أحمد
مناقش / أمانى ابراهيم يوسف
مناقش / عبدالله محمود فودة
الموضوع
Applied Medical Chemistry. Chemistry.
تاريخ النشر
2019.
عدد الصفحات
106 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الطب
تاريخ الإجازة
19/1/2019
مكان الإجازة
جامعة الاسكندريه - معهد البحوث الطبية - الكيمياء الطبية التطبيقية
الفهرس
Only 14 pages are availabe for public view

from 112

from 112

Abstract

Toxoplasmosis is a widespread infection caused by the obligate intracellular protozoan parasite T.gondii. Toxoplasmosis in immunocompetent people is usually asymptomatic or appears as flu-like symptoms, swollen lymph glands, muscle aches, and pain. The severity of toxoplasmosis partly depends on the T. gondii strain. It is usually classified as virulent and avirulent strains on the basis of pathogenicity in the mouse model. The virulent T. gondii strains have been maintained in mice to induce an acute infection. In contrast, the avirulent strain induces a chronic infection with development of cysts in the brains of these animals.
The SMX-TMP treatment of toxoplasmosis act as antiprotozoal associated to antioxidant in the treatment of toxoplasmosis which resulting on increased therapeutic efficacy and a reduction in cell injury.
MicroRNA-155 is relevant to T. gondii burden, plays a significant role in various physiological processes and its expression level changes dynamically during various immune responses in which T. gondii infection inhibit activation of macrophages and stimulate production of high levels of proinflammatory cytokines such as TNF-α.
BChE enzyme activity play important role as a marker for predicting the prognosis of diseases. The enzyme BChE actively participates in cholinergic neurotransmission,
immune response, acute infection and lipid metabolism.
ADA is the enzyme that irreversibly catalyzes the hydrolytic deamination of
adenosine to inosine. This enzyme is widely distributed in animal tissues. ADA activity has a critical role in the methylation process, cell growth and differentiation, apoptosis, DNA replication, and immune functions.
The present study aimed to detect the miRNA-155 expression, BChE and ADA activities in mice experimentally infected with virulent and avirulent strains of T. gondii.
The current study was conducted on ninety female Swiss Albino mice will be divided into four groups, as following:
 group (A): 10 mice took phosphate buffer saline and serve as a control group.
 group (B): 40 mice infected with avirulent strain of T.gondii.
 group (C): 10 mice infected with virulent strain of T.gondii.
 group (D): 30 mice infected with virulent strain of T.gondii and treated with SMX-TMP.
All Mice from group (B) sacrificed at different interval times (7, 27, 47, 67 days) p.i into four groups. Mice from group (C) sacrificed within one week or once upon the appearance of the disease. Mice from group (D) sacrificed at different interval times (5, 10, 20 days and before death p.i) into three groups. Liver collected and divided into two parts: The first part of the liver homogenated and used in molecular detection of mi-RNA-155 by real time-PCR and determined BChE, ADA activities and TNF-α level. The second part fixed in 10% formalin to perform histopathological examination.
A significant increase in the miRNA-155 expression in all liver of mice groups when compared with control group. A significant decreased in the miRNA-155 expression when compared virulent group (C) with vitulent-treated group (D) sacrificed at 20 days p.i and also significant decreased when compared avirulent group (B) sacrificed at 47 and 67 days p.i with 7 days p.i.
A significant decreased of BChE specific activity in liver of all mice groups of when compared with control group and a significant decreased when compared all groups sacrificed in different interval of avirulent group (B) with value at 7 days p.i as control. On other hand, asignificant increased of BChE specific activity when compared BChE in liver of virulent group (C) with vitulent-treated group (D) sacrificed at 20 days p.i.
A significant increase in ADA specific activity when compared the values of it with a value in mice groups with control group. A significant decreased in ADA specific activity when compared the value in virulent group (C) with vitulent-treated group (D) sacrificed at 20 days p.i and also significant decreased when compared with the value in avirulent group (B) sacrificed at 27 and 67 days p.i with 7 days p.i.
A significant increase in TNF-α concentration when compared the concenterations in the liver of mice groups with control group. A significant decreased in TNF-α concentration when compared the concenterations in liver of virulent group (C) with those of vitulent-treated group (D) sacrificed at 10, 20 days p.i and a significant decreased when compared a concenteration of TNF-α in avirulent group (B) sacrificed at 67 days p.i with concenterations at both 7 and 27 days p.i.
Generally, our results demonstrated a change in some parameters of the liver of T. gondii-infected mice, as well as signs of healing through using treatment with SMX-TMP. These results help to understand that some mechanisms involved in fighting the infection can be dangerous to the body itself, where the high expression level of miRNA-155 is due to it enhanced the proinflammatory response in chronic and acute phase toxoplasmosis then the expression decreased with treatment. The activity of BChE decreased due to the alteration can directly contribute to the pathogenesis of the disease which related to liver injury. On the other hand, ADA activity increased due to decreased adenosine levels, which contributes to the inflammatory process and tissue damage, because adenosine protects host cells from excessive tissue injury associated with severe inflammation. Supporting to all of the above TNF-α concenteration, it was increased. This may be due to the infection with T.gondii which caused induction of an immune response with production of pro-inflammatory and anti-inflammatory cytokines.
On the study of histopathologicalof livers of mice groups were supported the above results by:
group (B): avirulent infected mice and untreated, the liver sections revealed portal inflammation and the presence of intracellular tachyzoites and lytic necrosis in those sacrificed at 67 days p.i.
group (C): virulent infected mice and untreated, the liver section show multiple foci of necrosis.
group (D): virulent-treated group, the liver sections illusterates fibroplastic and proliferation of eosinophil and nuclear atypia as a sign of hepatocellular carcinoma.
This study concluded that the overexpression of hepatic miRNA-155 in T.gondii infected mice play an important role in the mechanism of regulating inflammation and immunity, the miRNAs may help better understand the mechanisms of host-parasite interactions, and highlight the potential of miRNAs in the diagnosis of toxoplasmosis. Also, the alterations in the BChE and ADA activities, as well as in the TNF-α levels in mice toxoplasmosis, suggesting that these alterations are very important in the inflammatory status.