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Immunoregulatory mechanisms of diethylcarbamazine in experimental autoimmune hepatitis and disease’s characterization on patients’ hepatic biopsies.
Universidade do Estado de Pernambuco (UPE)
Biological Science institute (ICB), University of Pernambuco. Avenue Agamenom Magalhães,Santo Amaro,Recife,Pernambuco,Brazil. CEP:50.100-130
Sura Wanessa Nogueira Santos Rocha
Sura Wanessa Nogueira Santos Rocha
English, Spanish and Portuguese
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
The hepatic diseases represent a major public health issue, compromising not only the wellbeing of an individual, but also the country’s economy. Having a wide range of etiologies, the hepatic chronic diseases have been attributed to a growth on morbidity reports. Between the most common causes of hepatic diseases, there are: excessive consumption of alcohol, viral hepatitis, and autoimmune process. Nevertheless, several therapeutic failures and pharmacological toxicity have been reported, creating the necessity to improve the conventional treatment by using hepatic tolerance mechanisms. In this context, diethylcarbamazine and N-acetylcysteine come up as potential anti-inflammatory drugs, with the possibility to ameliorate the inflammatory pattern.
What is the aim of the project?
The main objective of the project is to study the immunomodulator effect of the diethylcarbamazine and its association with N-acetylcysteine, in an experimental autoimmune hepatitis model, as well as to characterize this disease with patients’ hepatic samples from the Pernambuco Hepatic Institution, integrating the data to improve the disease’s management.
What techniques and methods are used?
The research methodology is based on both experimental and clinical study, in order to find an alternative treatment for autoimmune hepatitis. For this, it will be used scientific techniques and methods to help this whole process. In the experimental study, 70 male Balb mice, divided into 7 groups of 10, will be used. In 4 of them, autoimmune hepatitis will be induced and treated orally with N-acetylcysteine or Diethylcarbamazine for 12 days. Oral blood collection and fragments of liver, kidneys, pancreas and nervous system of the euthanized mice will be used for analysis in optical and electronic transmission microscopy, immunohistochemistry, Western Blot test and Reverse transcriptase polymerase chain reaction (RTqPCR). The clinical study will be based on an observational, analytical and retrospective study, using liver biopsy specimens from Liver Institute of Pernambuco (IFP). The samples under analysis are from patients, between 2010 and 2019, with possible diagnosis of autoimmune hepatitis, using the method of immunohistochemistry.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
- Follow-up of the experiments with all the lab team - Contention of mice, administration of N-acetylcysteine or Diethylcarbamazine in disease mice - Sample processing accomplishing the surgery in euthanized mice to take the liver, kidneys, pancreas and nervous system to analyse. - Realization of histological sections - Analyses of the samples in optical and electronic microscope - Immunohistochemistry - Participation and presentation of seminars Data analysis - Results of laboratory tests (Biopsies of human liver samples) - Analysis of medical records
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes. Seminars related to the main topic of the research will be organized during the exchange weeks. The articles are going to be selected in agreement with both professor and student. Furthermore, a workshop on mouse handling and restraint will also be provided on the start of the exchange.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student will prepare a presentation - The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Having knowledge on how to use a microscope.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system - Students in biomedical fields
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- ALTURFAN; E. I. et al. Protective effect of N-acetyl-L-cysteine against acrylamide-induced oxidative stress in rats. Vet. Anim. Sci. 36(4): 438-445; 2012
- FRANÇA MER; ROCHA SWS; OLIVEIRA WH; et al. Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis. Inflammopharmacology. 26(2):599-609; 2018
- LIBERAL et al. Autoimmune hepatitis: A comprehensive review. Jornal of Imunology; 41 126-139; 2013
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- PORTA; G. et al. Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings; histological profile; treatments; and outcomes. Jornal de pediatria; 2018
- RODRIGUES GB; OLIVEIRA EE; JUNIOR FJBM et al. Characterization and evaluation of nanoencapsulated diethylcarbamazine in model of acute hepatic inflammation.Int Immunopharmacol. 50:330-337; 2017
- ROCHA; S.W.S.; SANTOS; A.C.O.; SILVA; B.S.; OLIVEIRA et al. Effects of Diethylcarbamazine (DEC) on hepatocytes of C57BL/6J mice submitted protein malnutrition. Journal of food and drug analyses; 2012; 20; 524–531
- SAMUNI; Y. et al. The chemistry and biological activities of N-acetylcysteine. Biochimica et Biophysica Acta. 2013. 1880: 4117–4129
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