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.

  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.

  Former Heads And Staff Members


Former Heads of Laboratory

Late Prof. Dr./ Aisha Metwally: Founder-1995.

Prof. Dr./ Sanaa Botros: 1995-2008.

Prof. Dr./ Fatma Ebeid: 2008-2009.

Prof. Dr./ Madiha R. Mahmoud: 2009-2010.

Prof. Dr/ Naglaa M. El-Lakkany 2010-2019.

Staff Members 

Prof. Dr./ Abdel Nasser A. Sabra.

Researcher/ Rania A. khalaf.

Researcher/ Walaa Hamido El-Sayed.

Assistant Researcher/ Ahmed Said Hendawy.

Assistant Researcher/ Maha Badr Mohamed.

Pharmacist/ Abeer Ali Ebrahim El-Nagar.

Pharmacist/ Nourhan Mohamed Reffat Kamar. 

Pharmacist/ Sarah El-Rashdy Mostafa.

Pharmacist/ Amira Said Hendawy.

Pharmacist/ Hadeel Hesham Mohamed Elkattan.

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  Field of Research


Research staff at the Pharmacology Lab. 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 of vitro actives using whole animal experimentation where schistosomiasis infected animals is 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 commision (FP7 health programme).

Research staff at the Pharmacology Lab. have also been carrying out research work on pharmacodynamics/pharmacokinetics of antischistosomal 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 druggability of newly introduced drug candidates throughout discovery and development processes.
 

  Main Achievements


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 S. 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.

 

  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 calculation.

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).

 

  Laboratory Structure and Facilities


 

 

 

 

 

 

 

 

 

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  Training facilities


Evaluation of antischistosomal activity in vitro and in vivo in S. 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).

 

  Scope of Services


In vitro and in vivo evaluation of antischistosomal efficacy:

1. In vitro culture of worms and drug testing

2. Animal perfusion and worm recovery (ED50 estimation)

3. Tissue egg count

4. Percentage egg developmental stages (Oogram pattern)

Toxicity studies:

1. In vitro cytotoxicity assays on primary isolated hepatocytes and different cell lines (using MTT & SRB).

2. Acute toxicity (LD16, LD50 and LD84 estimation).

3. Subchronic and chronic toxicity.

Pharmacodynamics of drugs:

1. Determination of hepatic drug metabolism in animals by measuring drug metabolizing enzyme activities.

2. Biochemical and immunological aspects of drugs.

3. Evaluation of the hepatoprotective and antioxidant activities of drugs/compounds.

4. Evaluation of the antifibrotic effect of some drugs and measurement of tissue markers of liver fibrosis.

5. Safety of drugs used in liver diseases (liver and kidney function tests).

Pharmacokinetic studies 

1. Pharmacokinetics of antischistosomal drugs.

2. Evaluation of the bioavailability of drugs commonly prescribed to patients with chronic liver disease.

3. Determination of hepatic metabolic function using antipyrine clearance (APC).

 

  Projects


A- External Research Projects in the Last Ten Years:

1- Title:  Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases. (Project FP7 acronym: PDE4NPD).    Duration: 2014 - 2017.

Principal investigator: Prof. Dr. Sanaa Sabet Botros

2- Title: Development of new compounds with effect on Schistosomiasis (bilharzia)".

Financed Agency: SIDA.    Duration: 2009 - 2012.

Principal investigator: Prof. Dr. Sanaa Sabet Botros.

 

B- Internal Research Projects Financed by TBRI in the Last Ten Years:

1-Project No. 124 A (September 2018).

Potential modulating effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) on liver fibrosis in NAFLD diabetic rats. 

Principal investigator: Prof. Dr. Naglaa Mohamed El-Lakkany.

2- Project No. 117 A (Februray 2018).

Title: Impact of short chain fatty acids (SCFA) production adjustment using gut microbiota alone or in combination with metformin on modulation of autophagy and insulin resistance in non-alcoholic fatty liver disease-induced rats.

Principal investigator: Prof. Dr. Sayed Hassan Seif el-Din.

3- Project No. 116 A (January 2018)

Title: Pharmacodynamics of Synriam alone and in combination with a cytochrome P450 inhibitor (ketoconazole) against juvenile and mature schistosomiasis in experimental animals.

Principal investigator: Prof. Dr. Abdel- Nasser Abdel- Aal Sabra.

4- Project No. 101 A (March 2013-until now).  

Title: Possible anti-inflammatory activity of certain natural products against hepatic inflammation in experimental animals and evaluation of their safety in hepatocyte cultures.

Principal investigator: Prof. Dr. Sayed Hassan Seif el-Din

5- Project No. 99 A (2012- until now).  

Title: Possible antifibrotic effects of some natural and synthetic compounds against experimental hepatic fibrogenesis: in vitro and in vivo study.

Principal investigator: Prof. Dr. Naglaa Mohamed El-Lakkany.

6- Project No. 95 A (2010-2018).  

Title: Evaluation of the efficacy of insulin-sensitizing and lipid lowering agents with ontioxidants in management of experimental non-alcholic fatty liver disease.

Principal investigator: Prof. Dr. Fatma Abdel Latif Ebeid.

7- Project No. 83 A (2009-2018).

Title: Pharmacokinetic of drugs commonly used by patients with chronic liver disease.

Principal investigator: Prof. Dr. Sanaa Sabet Botros

8- Project No. 82 A (2006- 2011).  

Title: Evaluation of antifibrotic and antioxidant drugs with or without praziquantel in murine schistosomiasis mansoni.

Principal investigator: Prof. Dr. Fatma Abdel Latif Ebeid.

  Publications


1. Botros SS, El-Lakkany NM, Seif El-Din SH, William S, Sabra AN, Hammam OA, de Koning HP (2020). The phosphodiesterase-4 inhibitor roflumilast impacts Schistosoma mansoni ovipositing in vitro but displays only modest antischistosomal activity in vivo. Exp Parasitol. 208:107793.

2. El-Maadawy WH, Hammam OA, Seif El-Din SH, El-Lakkany NM (2020). α-Lipoic acid modulates liver fibrosis: A cross talk between TGF-β1, autophagy, and apoptosis. Hum Exp Toxicol 39(4): 440450.

3. Sebastian-Perez V, García-Rubia A, Seif El-Din SH, Sabra AA, El-Lakkany NM, William S, Blundell TL, Maes L, Martinez A, Campillo NE, Botros SS, Gil C (2020). Deciphering the enzymatic target of a new family of antischistosomal agents bearing a quinazoline scaffold using complementary computational tools. J Enzyme Inhib Med Chem  35(1): 511523.

4. El-Lakkany NM, El-Maadawy WH, Seif El-Din SH, Saleh S, Safar MM, Ezzat SM, Mohamed SH, Botros SS, Demerdash Z, Hammam OA (2019). Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study. J Tradit Complement Med 9(1): 45-53.

5. Radwan A, El-Lakkany NM, William S, El-Feky GS, Al-Shorbagy MY, Saleh S, Botros S (2019). A novel praziquantel solid lipid nanoparticle formulation shows enhanced bioavailability and antischistosomal efficacy against murine S. mansoni infection. Parasit Vectors. 12(1):304.

6. Ghareeb MA, Sobeh M, El-Maadawy WH, Mohammed HS, Khalil H, Botros S, Wink M. chemical profiling of polyphenolics in Eucalyptus globulus and evaluation of its hepato-renal protective potential against cyclophosphamide-induced toxicity in mice. Antioxidants (Basel) 2019; 8(9): pii: E415.

7. Botros SS, William S, Sabra AA, El-Lakkany NM, Seif El-Din SH, García-Rubia A, Sebastián-Pérez V, Blaazer AR, de Heuvel E, Sijm M, Zheng Y, Salado IG, Munday JC, Maes L, de Esch IJP, Sterk GJ, Augustyns K, Leurs R, Gil C, De Koning HP (2019). Screening of a PDE-focused library identifies imidazoles with in vitro and in vivo antischistosomal activity. Int J Parasitol Drugs Drug Resist. 9:35-43.

8. El-Lakkany NM, El-Maadawy WH, Seif el-Din SH, Hammam O, Mohamed SH, Ezzat SM, Safar MM, Saleh S (2017). Rosmarinic acid attenuates hepatic fibrogenesis via suppression of hepatic stellate cell activation/proliferation and induction of apoptosis. Asian Pac J Trop Med 10(5):444-53. Sanaa S. Botros, Naglaa M, El Lakkany, Olfat A Hammam, Abdel Naser A. Sabra, Alaa A.Taha (2016). Possible carcinogenic potential of dimethyl dimethoxybiphenyl dicarboxylate in experimental animals. J Adv Pharm Technol Res, 7:54-8.

9. El-Lakkany NM, Hendawy AS, Seif el-Din SH, Ashour AA, Atta R, Abdel-Aziz AH, Mansour AM, Botros SS (2016). Bioavailability of paracetamol with/without caffeine in Egyptian patients with hepatitis C virus. Eur J Clin pharmacol, 72(5):573-82.

10. Sayed Hassan Seif el-Din, Naglaa Mohamed El-Lakkany, Maha Badr Salem, Olfat Ali Hammam, Samira Saleh, Sanaa Sabet Botros (2016). Resveratrol mitigates hepatic injury in rats by regulating oxidative stress, nuclear factor-kappa B and apoptosis. J Adv Pharm. Technol Res,7: 99-104.

11. El-Lakkany NM, Seif El-Din SH, Sabra AA, Hammam OA, Ebeid FA (2016). Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver. Res Pharm Sci, 11(5): 374-382.

12. Ezzat SM, Salama MM, Seif El-Din SH, Saleh S, El-Lakkany NM, Hammam OA, Salem MB, Botros SS (2016). Metabolic profile and hepatoprotective activity of the anthocyanin-rich extract of Hibiscus sabdariffa calyces. Pharm Biol, 54(12):3172-3181.

13. Seif el-Din SH, El-Lakkany NM, El-Naggar AA, Hammam OA, Abd El-Latif HA, Ain-Shoka AA, Ebeid FA (2015). Effects of rosuvastatin and/or β-carotene on non-alcoholic fatty liver in rats. Res Pharm Sci, 10(4): 275287.

14. El-Feky GS, Mohamed WS, Nasr HE, El-Lakkany NM, Seif el-Din SH, Botros SS (2015).  Praziquantel in a clay nanoformulation shows more bioavailability and higher efficacy against murine Schistosoma mansoni infection. Antimicrob Agents Chemother, 59(6): 35013508.

15. El-Sayed S. Abdel-Hameed, Salih A. Bazaid, Abdel Nasser A. Sabra (2015). Total phenolic, in vitro antioxidant activity and safety assessment (Acute, sub-chronic and chronic toxicity) of industrial Taif rose water by-product in mice. Der Pharmacia Lett, 7 (2):251-259.