Pharmacology Department

Mission


To promote research and development to investigate current and newly introduced compounds/drugs for better management of endemic diseases. To prepare distinguished, highly qualified and specialized pharmacologists equipped with the knowledge, skills and values required to perform scientific research at the highest international standards.

Vision


To provide a distinctive level in scientific research through cutting-edge research and to fulfill the technological and scientific research needs of pharmaceutical industries, governmental and community requirements. To be prestigious locally, nationally and internationally, as a department of a prestigious institution, in the research and development of health products.

Research Fields


Research fields

Research staff  at the Pharmacology Department have been carrying out research work on efficacy/resistance of antischistosomal drugs since > 30 years, at the national and international levels, including:

  • The in vitro testing of potential antischistosomal activity (EC50).
  • In vivo testing using whole animal experimentation where schistosomiasis infected animals are used to study parasitological criteria of cure.
  • Inter-relation between antischistosomals and the immunological status of the host.
  • Resistance to praziquantel treatment and to re-infection after cure as emerging problems.
  • The use of new formulations of the antischistosomal drug “praziquantel” in a way to overcome its drawbacks.

In this respect, we have successfully completed and running collaborative research projects with national and international agencies e.g. UNEP, US-AID, US-NIH, EU, Academy of Sciences of the Czech Republic, Swiss Tropical Institute (STI), Switzerland, Swedish International Cooperation Development Agency (SIDA) and European commission (FP7 health programme).

Research staff at the Pharmacology Department have also been carrying out research work on pharmacodynamics/pharmacokinetics of anti-schistosomal and hepatoprotective drugs including:

  •            Assessment of drug bioavailability/pharmacokinetics using HPLC.
  • Acute and chronic toxicity studies.
  • Assessment of hepatic drug-metabolizing and antioxidant enzymes.
  • Conventional liver functions and assessment of liver fibrotic biomarkers.
  • Research for new therapeutic options for treating NAFLD/NASH.
  • Cytotoxicity assays of drugs/compounds using isolated and cultured primary hepatocytes.
  • Determination of drug/herb-drug interactions using cytochrome-P450 isoforms.
  • Examination of the antifibrotic potential of drugs/compounds using isolated hepatic stellate cells (HSCs) and cultured HSC-T6 cell line.
  • Characterization of ADME–Tox profiles of compounds through in vitro and in vivo approaches to predict early drug ability of newly introduced drug candidates throughout discovery and development processes.

 


Structure


Structure

DEPARTMENT STRUCTURE AND FACILITIES

One main big and two small laboratories are equipped with basic facilities:

Electronic balances, water baths, microscopes, centrifuges, oven, spectrophotometers, autoclave, water distillator, high-speed centrifuge, pumping machines, liquid nitrogen, ELISA reader, tissue homogenizers, sonicator, three vertical deep freezers (-30°C & -80 °C), two laminar flow, two CO2 incubator, cooling centrifuge, inverted microscope and two HPLC, plethysmometer and hot cold plate. Since 2009, Pharmacology Department has established a new unit (in place of one small laboratory) under the name “Drug Evaluation and Discovery Unit (DEDU)” (under supervision of Prof. Sanaa Botros). Pharmacology Department and its unit has been assigned (2011) by WHO-ANDI an excellence center on antitrematodal R&D.

 


Techniques


Techniques

    RUNNING TECHNIQUES

    In vitro evaluation of antischistosomal efficacy:

    • The primarily screen is conducted using the in vitro worm killing.
    • Estimation of compound EC50 using in vitro actives in the primarily screen.

    In vivo evaluation of antischistosomal efficacy:

    • In vivo evaluation of antischistosomal activity including worm burden, sex distribution, tissue egg load and percentage egg developmental stages and ED50.

    Toxicity studies:

    • In vitro cytotoxicity assays on primary isolated hepatocytes and different cell lines (using MTT & SRB).
    • Conventional toxicity testing (LD16, LD50 and LD84 estimation).

    Pharmacodynamics of drugs:

    • Evaluation of drug metabolizing enzyme activities.
    • Biochemical and immunological aspects of drugs.
    • Evaluation of the hepatoprotective and antioxidant activities of drugs/compounds.
    • Evaluation of the antifibrotic effects of drugs.
    • Safety of drugs used in liver diseases (liver and kidney function tests).

    Pharmacokinetic studies:

    • Pharmacokinetics of antischistosomal drugs (e.g. Praziquantel).
    • Evaluation of the bioavailability of drugs commonly prescribed to patients with chronic liver disease (e.g. pracetamol).
    • Determination of hepatic metabolic function using antipyrine clearance (APC).

     


Work In Progress


Running Facilities

  • Evaluation of antischistosomal activity in vitro and in vivo in mansoni and S. haematobium infected animals.
  • Determination of cardinal parameters of acute toxicity (ED16, ED50 & ED84) for new drugs/compounds.
  • Determination of short chronic and chronic toxicity and examination of blood biochemical changes.
  • Determination of drug metabolizing enzyme (CYP450 and cyt b5) activities.
  • Evaluation of drugs bioavailability using HPLC and assessment of pharmacokinetic parameters.
  • Assessment of the antioxidant enzymes.
  • Evaluation of hepatic metabolic functional status in patients with chronic liver disease using antipyrine clearance.
  • In vitro cytotoxicity assays on primary isolated hepatocytes and different cell lines (using MTT & SRB. 


Services


SCOPE OF SERVICES

In vitro and in vivo evaluation of antischistosomal efficacy:

  • In vitro culture of worms and drug testing
  • Animal perfusion and worm recovery (ED50 estimation)
  • Tissue egg count
  • Percentage egg developmental stages (Oogram pattern)

Toxicity studies:

  • In vitro cytotoxicity assays on primary isolated hepatocytes and different cell lines (using MTT & SRB).
  • Acute toxicity (LD16, LD50 and LD84 estimation).
  • Subchronic and chronic toxicity.

Pharmacodynamics of drugs:

  • Determination of hepatic drug metabolism in animals by measuring drug metabolizing enzyme activities.
  • Biochemical and immunological aspects of drugs.
  • Evaluation of the hepatoprotective and antioxidant activities of drugs/compounds.
  • Evaluation of the antifibrotic effect of some drugs and measurement of tissue markers of liver fibrosis.
  • Safety of drugs used in liver diseases (liver and kidney function tests).

Pharmacokinetic studies:

  • Pharmacokinetics of antischistosomal drugs.
  • Evaluation of the bioavailability of drugs commonly prescribed to patients with chronic liver disease.
  • Determination of hepatic metabolic function using antipyrine clearance (APC).

Thesis


Staff M.Sc. &Ph.D. thesis

M.Sc. Thesis

  1. In vitro study of the influence of acetaminophen on the response of the cardiovascular system to catecholamines. Dr/ Sanaa S. Botros (1976).
  2. The effect of antibilharzial drugs on protein metabolism. Dr/ Fatma A. Ebeid (1980).
  3. The Possible involvement of angiotensin converting enzyme inhibitor in the therapy of schistosomiasis mansoni. Dr/ Madiha R. Mahmoud (1989).
  4. Studies of some factors which may affect the blood level of praziquantel in experimental animals. Dr/ Naglaa M. El-Lakkany (1997).
  5. Effects of praziquantel on some aspects of drug-metabolizing capacity in Schistosoma mansoni-infected mice. Dr/ Sayed H. Seif el-Din (1999).
  6. Effect of combined immunotherapy and chemotherapy on susceptibility to Schistosoma mansoni infection in mice. Dr./ Abdel-Nasser A. Sabra (1999).
  7. Assessment of hepatic metabolic function in patients with chronic liver disease. Res. / Rania Khalaf Abdel-Kader (2006).
  8. Possible protective effects of losartan and Silymarin on liver fibrosis in murine Schistosoma mansoni. Res./ Walaa Hamido El-Sayed (2010).
  9. Effect of an insulin sensitizer agent, lipid lowering agent and an antioxidant on non-alcoholic Fatty Liver in rats. Pharmacist/ Abeer Ali Ebrahium EL-Naggar (2015).
  10. Pharmacokinetic study of paracetamol alone or in combination with caffeine in patients with chronic liver disease. Res./ Ahmed Said Hendawy (2016).
  11. Effect of certain compounds with possible anti-inflammatory activity on hepatic metabolizing enzymes in experimental animals. Res./ Maha Badr Mohamed (2016).
  12. Investigation of potential impact of gossypol on the antitumor efficacy of ponatinib on experimental solid Ehrlich carcinoma and some human liver/gastrointestinal cancer cell lines. Pharmacist/ Hadeel Hesham (2022).

Ph.D. Thesis

  1. Immunosuppressive ability of antischistosomal drugs in experimental animals. Dr/ Sanaa S. Botros (1980).
  2. Studies on the effect of treatment on amino acid metabolism in experimental schistosomiasis. Dr/ Fatma A. Ebeid (1984).
  3. Studies of the effect of a new anti-inflammatory drug on the liver arachidonic acid metabolites in schistosomiasis mansoni. Dr/ Madiha R. Mahmoud (1997).
  4. Effect of immunotherapy as adjuvant on the response to praziquantel treatment in mice infected with a Schistosoma mansoni-resistant isolate. Dr/ Naglaa M. El-Lakkany (2003).
  5. Evaluation of concerted usage of antioxidants and praziquantel in treatment of Schistosoma mansoni-infected mice. Dr/ Sayed H. Seif el-Din (2003).
  6. Influence of therapeutic pressure of praziquantel quantitatively and qualitatively on further selection of insusceptible Schistosoma mansoni isolates in mice. Dr/ Abdel-Nasser A. Sabra (2003).
  7. Influence of hepatotoxic compounds on the molecular changes as well as DNA repairing mechanisms in hepatocytes./ Rania Khalaf Abdel-Kader (2014).
  8. Potential antifibrotic effects of some natural compounds against experimental hepatic fibrogenesis. / Walaa Hamido El-Maadawy (2017).
  9. Effect of lactobacillus/metronidazole alone or in combination with metformin in rats with non-alcoholic fatty liver: possible modulation of gut short chain fatty acids and autophagy. / Maha Badr (2020).
  10. Potential modulatory effect of vildagliptin on experimentally induced high fat diet-liver fibrosis in diabetic rats./ Ahmed Said Hendawy (2022).

Awards


Achieved staff awards

Prof. Dr./ Sanaa Sabet Botros:
Theodor Bilharz Research Institute Appreciation Award (2014).

Prof. Dr./ Naglaa Mohamed El-Lakkany:
The Late Professor Sawsan Omran’s Award for The Best Research Article for the Year 2011.
Theodor Bilharz Research Institute Excellence Award (2015).

Prof. Dr./ Sayed Hassan Seif el-Din
The Late Professor Sawsan Omran’s Award for The Best Research Article for the Year 2012.
Theodor Bilharz Research Institute Excellence Award (2016).

Res./ Walaa Hamido El-Maadawy
Theodor Bilharz Research Institute Encouragement Award (2021).

Res./ Maha Badr
Theodor Bilharz Research Institute Best Research Article extracted from PhD thesis Award for the Year (2021).

Acheivments


MAIN ACHEIVMENTS

  • Reducing the cost of schistosomiasis treatment and hence socioeconomic needs of the country, the local Egyptian brand of the antischistosomal drug praziquantel “Distocide” has been examined and was found to possess equal efficacy and bioavailability to that of the foreign imported one “Biltricide”.
  • Cocktails of antischistosomals in reduced doses and antischistosomals with vaccines led to enhanced drug antischistosomal efficacy and lessened schistosomiasis morbidity.
  • Avoiding set back of schistosomaiasis control measures not only at the level of Egypt but also at the African level, lack of evidence for an antischistosomal activity of Mirazid; an Egyptian antischistosomal drug newly introduced to Arab and African countries has been demonstrated.
  • Because the international scientific community has been left with one antibilharzial drug “praziquantel”, the phenomenon of resistance to this only available drug in African countries (Egypt, Cameroon and Senegal), and the identification in the field of schistosome isolates that possess variable sensitivity to the drug have been demonstrated, urging the pharmaceutical industry to search for new chemotherapeutic alternatives and WHO to monitor for the response to this sole antischistosomal on a regular systematic basis.
  • For the first time, the efficacy of the group of acyclic nucleotide analogues 9-(S)[3-hydroxy-2-(phosphonomethoxy) propyl] adenine [(S)-HPMPA] against a wide range of schistosome life cycle specially the schistosome egg, the main cause of schistosomiasis  morbidity, has been revealed.
  • The efficacy of the antimalarial drugs “artemether, mefloquine and halofantrine” as antischistosomals against not only the immature stages of the Egyptian strain of mansoni but also the mature ones.
  • Antipyrine clearance using HPLC expressed the least hepatic impairment compared to conventional liver functions.
  • Miracidial response to antischistosomal drugs has been recommended as a simple inexpensive quick biological test for efficacy/resistance to antischistosomal drugs.
  • Advice to the scientific community against the use of yellow pills (Dimethyl Diphenyl Bicarboxylate; DDB) popularly used by all viral hepatitis patients and claimed to improve liver functions markedly; liver functions of viral hepatitis patients under this treatment were not genuinely improved using the sensitive antipyrine clearance.
  • Efficacy of AT1-receptor blockers (losartan) and silymarin against S. mansoni -induced liver fibrosis was recommended.

Publications

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  • Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s,
  • Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s,
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Projects

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  • Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s,
  • Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s,
  • Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s,
  • Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s,
  • Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s,
Staff

Department Staff Members