Vision


 To establish a leading pharmacologists platform for the recognition 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

  Head of the Laboratory


Prof. Sayed Hassan Seif El-Din
E mail: s.seifeldin@tbri.gov.eg
            sayedseifeldin@hotmail.com

  Former Heads And Staff Members


Former Heads 

Prof. Naglaa M. El-Lakkany

Late Prof. Aisha Metwally

Emeritus Prof. Sanaa Sabet Botros

Emeritus Prof. Fatma A. Ebied

Prof. Madiha Mahmoud

 

Staff Members 

 

Prof. Sayed Seif el-Din

Prof. Abdel Nasser Sabra

Researcher Rania khalaf.

Researcher Walaa Hamido El-Maadawy

Assistant Researcher Ahmed Said Hendawy

Assistant Researcher Maha Badr Mohamed

Pharmacist Abeer Ali Ebrahium El-Naggar

Pharmacist Nourhan Mohamed Reffat Kamar

Pharmacist Sarah El-Rashdy Mostafa

  Field of Research


  1. Efficacy/resistance of antischistosomal drugs:
  2. Pharmacodynamics/pharmacokinetics of drugs specifically antischistosomal and hepatoprotectives
  3. Compounds ADME–Tox profiles to predict early drugability of newly introduced drug candidates.
  4. Innovative therapeutic options for fatty liver disease and liver fibrosis.

  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” was found to possess equal efficacy and bioavailability to that of the foreign imported one “Biltricide”. Accordingly, the local brand has been the one in use in the local market since 1992.

·    Cocktails of antischistosomals in reduced doses and antischistosomals with vaccines led to enhanced drug antischistosomal efficacy and lessened schistosomiasis morbidity.

·    Avoidance of 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.

·    Demonstration of the stable efficacy of Praziquantel (PZQ); the only available antischistosomal, after a decade of drug pressure and despite the recognition of compromised biological fitness of field S. mansoni isolates with diminished sensitivity to PZQ.

·    For the first time, revelation of the efficacy of the 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, which is considered the main cause of schistosomiasis  morbidity.

·    Determination of 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.

·    Application of the antipyrine clearance test "using HPLC" as an assessment method for the hepatic metabolic functions in patients with chronic liver disease, which expresses the least hepatic impairment when compared to conventional liver functions.

·    Recommendation of miracidial response to antischistosomal drugs 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), which was 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.

·    Demonstration of efficacy of AT1-receptor blockers (losartan) and silymarin against S. mansoni -induced liver fibrosis.

      Accomplishment of international collaborative research projects, including UNEP-ASRT (1984-1988), USAID-Egyptian Ministry of Health, (1990-1994;  1992-1995 and1995-1998), NIH-USA, (1998-2001), Academy of Sciences of the Czech Republic and the Academy of Sciences of the Arab Republic of Egypt, (2001-2003), INCO-DEV, (2001-2004), European Commission (2003-2006) and SIDA, 2009-2011.

  Running Techniques


               a. In vitro evaluation of antischistosomal efficacy:

  • Schistosome worm killing
  • Estimation of compound EC50
  1. In vivo evaluation of antischistosomal efficacy using S. mansoni infected animals:
  • Estimation of the parasitological criteria of cure including worm burden, sex distribution, tissue egg load, percentage egg developmental stages and ED50 calculation.
  • Estimation of the inter-relation between antischistosomals and the immunological status of the host.
  1. Toxicity studies:
  • In vitro cytotoxicity assays on primary isolated hepatocytes and different cell lines (using MTT & SRB).
  • Conventional in vivo toxicity assays e.g: the three cardinal parameters of acute toxicity (LD16, LD50 and LD84), sub-chronic and chronic toxicity.
  1. Pharmacodynamics/ Pharmacokinetic studies:
  • Pharmacokinetics,  bioavailability  and bioequivalence of compounds/drugs
  • Evaluation of hepatic drug metabolizing and antioxidant enzymes activities.
  • Assessment of innovative  formulations of established drugs using nanotechnology to overcome known drawbacks.
  • Investigation of innovative therapeutic options for fatty liver disease.
  • Estimation of hepatoprotective and antifibrotic potential of drugs/compounds.
  • Determination of hepatic metabolic function using antipyrine clearance (APC) as well as conventional liver function assays
  • Detection of biochemical and immunological aspects of drugs.

 

Estimation of Drug/herb-drug interactions using cytochrome-P450 isoforms.

  Laboratory Structure and 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 flows, two CO2 incubators, cooling centrifuge, inverted microscope and two HPLC, plethysmometer and hot cold plate. Since 2009, pharmacology Lab. has established a "Drug Evaluation and Discovery Unit (DEDU)” (supervisioned  by Prof. Sanaa Botros) has been assigned by WHO-ANDI an excellence center on antitrematodal R&D.

  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 subchronic 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 conventional hepatic metabolic functions

· In vitro cytotoxicity assays using primary isolated hepatocytes and cell lines (using MTT & SRB)

  Projects


 External projects:

 

SIDA (2009 – 2012): Development of new compounds with effect on Schistosomiasis (bilharzia)". PI: Prof. Sanaa Sabet Botros.     

Project FP7 acronym, PDE4NPD (2014 - 2017): Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases. PI: Prof. Sanaa Sabet Botros.   

 

 Internal projects:  

 Pharmacokinetic of drugs commonly used by patients with chronic liver disease. PI: Prof. Sanaa Sabet Botros (2009)    

Evaluation of the efficacy of insulin-sensitizing and lipid lowering agents with antioxidants in management of experimental non-alcoholic fatty liver disease. PI: Prof. Fatma Abdel Latif Ebeid (2010)   

Possible antifibrotic effects of some natural and synthetic compounds against experimental hepatic fibrogenesis: in vitro and in vivo study. PI: Prof. Naglaa Mohamed El-Lakkany (2012)   

Possible anti-inflammatory activity of certain natural products against hepatic inflammation in experimental animals and evaluation of their safety in hepatocyte cultures. PI: Prof. Sayed Hassan Seif el-Din (2013).  

  Publications


Sabra AN, Botros S (2008). Response of Schistosoma mansoni isolates having different drug sensitivity to praziquantel over several life cycle passages with and without therapeutic pressure. J Parasitol, 94(2): 537-541.

Botros SS, Hammam OM, El-Lakkany NM, Seif el-Din SH, Ebeid FA (2008). Schistosoma haematobium (Egyptian strain): Rate of development and effect of praziquantel treatment. J Parasitol, 94: 386-394.

Botros SS, Sabra A, William S (2008). Miracidial assay as a simple, inexpensive biological test for sensitivity to praziquantel (PZQ) using field and laboratory PZQ-susceptible and insusceptibleSchistosoma mansoni isolates. Aust J Basic Appl Sci, 2: 677-684. 

Doenhoff MJ, Hagan P, Cioli D, Southgate V, Pica-Mattocia L, Botros SS, Coles G, Tchuem-Tchuente LA, Mbaye A, Engeles D (2009). Praziquantel: Its use in control of schistosomiasis in sub-Saharan Africa and current research needs. Parasitology, 13: 1-11.

Botros SS, El-Lakkany NM, Badawy AA, Mahmoud SS, Ebeid FA, Fenwick A (2009). Mirazid shows insignificant activity against ovine fascioliasis. Ann Trop Med Parasitol, 103(7):1-12.

Botros S, El-Lakkany N, Seif el-Din S, Sabra A, Ibrahim M (2011). Comparative efficacy and bioavailability of different praziquantel brands. Exp Parasitol, 127: 515-521.

Seif el-Din SH, Al-Hroob AM, Ebeid FA (2011). Schistosoma mansoni: N-Acetylcysteine downregulates oxidative stress and enhances the antischistosomal activity of artemether in mice. Exp Parasitol, 128: 230-235.

El-Lakkany N, Seif el-Din S, Ebeid F (2011). The use of pentoxifylline as adjuvant therapy with praziquantel downregulates profibrogenic cytokines, collagen deposition and oxidative stress in experimental schistosomiasis mansoniExp Parasitol, 129:152–157.

Keiser J, Sayed H, El-Ghanam M, Sabry H, Anani S, El-Wakeel A, Hatz C, Utzinger J, Seif el-Din S, El-Maadawy W, Botros S (2011). Efficacy and safety of artemether in the treatment of chronic fascioliasis in egypt: exploratory phase-2 trials. PLoS Neglec Trop Dis, 5(9): e1285.

El-Lakkany NM, El-Maadawy W, Ain-Shoka A, Badawy A, Hammam O, Ebeid F (2011).Potential antifibrotic effects of AT1 receptor antagonist, losartan, and⁄or praziquantel on acute and chronic experimental liver fibrosis induced by Schistosoma mansoniClin Exp Pharmacol Physiol, 38: 695-704.

El-Lakkany NM, Seif el-Din SH, Sabra AA, Hammam OA (2011). Pharmacodynamics of mefloquine and praziquantel combination therapy in mice harbouring juvenile and adult Schistosoma mansoniMem Inst Oswaldo Cruz, 106(7): 814-822.

El-Lakkany NM, Hammam O, El-Maadawy W, Ain-Shoka A, Badawy A, Ebeid F (2012). Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis. Parasit Vectors, 5: P 1-14.

El-Lakkany N, Seif el-Din S, Heikal L (2012). Bioavailability and in vivo efficacy of a praziquantel–polyvinylpyrrolidone solid dispersion in Schistosoma mansoni-infected mice. Eur J Drug Metab Pharmacokinet, 37: 289-299.

Liu H, William S, Herdtweck E, Botros S, Dömling A (2012). MCR synthesis of praziquantel derivatives. Chem Biol Drug Des, 79: 470-7.

El-Lakkany NM, Seif el-Din SH, Sabra AA, Ebeid FA, Botros SS (2012). Changes in hepatic phase-I and -II drug-metabolizing enzymes and antioxidant capacity in Egyptian ovine fascioliasis treated with triclabendazole. Global J Pharmacol, 6: 199-207.

Nwaka S, Ochem A, Besson D, Ramirez B, Fakorede F, Botros S, Inyang U, Mgone C, Adae-Mensah I, Konde V, Nyasse B, Okole B, Guantai A, Loots G, Atadja P, Ndumbe P, Sanou I, Olesen O, Ridley R, Ilunga T (2012). Analysis of pan-African Centres of excellence in health innovation highlights opportunities and challenges for local innovation and financing in the continent.BMC Int Health Hum Rights, 27:11.

Seif el-Din SH, Sabra AA, Hammam OA, El-Lakkany NM (2013). Effect of ketoconazole, a cytochrome p450 inhibitor, on the efficacy of quinine and halofantrine against adult schistosoma mansoni in mice. The Korean J Parasitol, 51(2): 165-175.

El-Lakkany NM, Seif el-Din SH (2013). Haemin enhances the in vivo efficacy of artemether against juvenile and adult Schistosoma mansoni in mice. Parasitol Res, 112(5):2005-2015.

Seif el-Din SH, El-Lakkany NM, Mohamed MA, Hamed MM, Sterner O, Botros SS (2014).Potential effect of the medicinal plants Calotropis proceraFicus elastica and Zingiber officinaleagainst Schistosoma mansoni in mice. Pharm Biol, 52(2):144-150.

William S, Saad A, Abdou A, Refahy L, Sabra A, Sterner O, Botros S (2014). Potential antischistosomal activities of some Egyptian native plants using Schistosoma mansoni worm killing assay. Global J Pharmacol, 8(2): 237-244.

Al-Sayed E, El-Lakkany NM, Seif, el-Din SH, Sabra AA, Hammam OA (2014). Hepatoprotective and antioxidant activity of Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in mice. Pharm Biol, 52(12):1581-1590.

Sherif SA, Moharib MN, El-Lakkany NM, Hammam OA, Salman FH, El-Naggar MM (2014). The use of microencapsulated hepatocytes transplantation reduces mortality and liver alterations inSchistosoma mansoni infected hamsters. J Egypt Soc Parasitol, 44(1): 229-242.

Al-Sayed E, Martiskainen O, Seif el-Din SH, Sabra AA, Hammam OA, El-Lakkany NM, Abdel-Daim MM (2014). Hepatoprotective and antioxidant effect of Bauhinia hookeri extract against carbon tetrachloride-induced hepatotoxicity in mice and characterization of its bioactive compounds by HPLC-PDA-ESI-MS/MS. BioMed Res Int, doi.org/10.1155/2014/245171.

Seif El-Din SH, Sabra AA, Hammam OA, Ebeid FA, El-Lakkany NM (2014). Pharmacological and antioxidant actions of garlic and/or onion in non-alcoholic fatty liver disease (NAFLD) in rats. J Egypt Soc Parasitol, 44(2): 295-308.

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.

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.

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.

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.

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.

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.

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.

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 ofHibiscus sabdariffa calyces. Pharm Biol, 54(12):3172-3181.

El-Lakkany NM, El-Maadawy WH, Seif El-Din SH, Hammam OA, 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):444-453.

El-Lakkany NM, El-Maadawy WH, Seif el-Din SH, Saleh S, Safar MM, Shahira M. Ezzat SM, Mohamed SH, Botros SS, Demerdash Z, Hammam OA. Antifibrotic effects of gallic acid on hepatic stellate cells: in vitro and in vivo mechanistic study. J Tradit Complement Med, in press.