Browsing by Author "Botros S.S."

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    Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study
    (National Taiwan University, 2019) El-Lakkany N.M.; El-Maadawy W.H.; Seif el-Din S.H.; Saleh S.; Safar M.M.; Ezzat, Shahira M; Mohamed S.H.; Botros S.S.; Demerdash Z.; Hammam O.A.; Department of Pharmacology; Theodor Bilharz Research Institute; Warak El-Hadar; Imbaba P.O. Box 30; Giza; 12411; Egypt; Department of Pharmacology and Toxicology; Faculty of Pharmacy; Cairo University; Cairo; 11562; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; Cairo University; Cairo; 11562; Egypt; Department of Immunology; Theodor Bilharz Research Institute; Warak El-Hadar; Imbaba P.O. Box 30; Giza; 12411; Egypt; Department of Pathology; Theodor Bilharz Research Institute; Warak El-Hadar; Imbaba P.O. Box 30; Giza; 12411; Egypt; Department of Pharmacology and Biochemistry; Faculty of Pharmacy; The British University in Egypt; Suez Desert Road; P.O. Box 43; ElSherouk City; Cairo 11837; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); 6th of October; Giza; 12566; Egypt
    Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotective and antioxidant activities. Accordingly, this study investigated the antifibrotic effects of GA through clarifying its mechanisms on hepatic stellate cells� (HSCs) activation, proliferation and/or apoptosis. In vitro effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. In vivo, hepatic fibrosis was induced via chronic thioacetamide (TAA)-intoxication. TAA-intoxicated rats were treated with silyamrin or GA. At end of experiment, liver functions, hepatic MDA, GSH, PDGF-BB, TGF-?1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (?-SMA), proliferating cellular nuclear antigen (PCNA) and caspase-3 were examined. In vitro, GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC50= 45 and 19 ?g/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. In vivo, GA reduced ALT, AST, MDA, PDGF-BB levels, collagen deposition and fibrosis score (S1 vs S4); increased caspase-3 expression and restored GSH stores, TGF-?1 level, ?-SMA and PCNA expressions. In conclusion, GA counteracted the progression of hepatic fibrosis through reduction of HSCs proliferation/activation mutually with their apoptosis induction. � 2018 Center for Food and Biomolecules, National Taiwan University
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    Praziquantel in a clay nanoformulation shows more bioavailability and higher efficacy against murine Schistosoma mansoni infection
    (American Society for Microbiology, 2015) El-Feky G.S.; Mohamed W.S.; Nasr H.E.; El-Lakkany N.M.; Seifel-Din S.H.; Botros S.S.; Department of Pharmaceutics; Faculty of Pharmacy; October University for Modern Sciences and Arts; Cairo; Egypt; Department of Pharmaceutical Technology; National Research Center; Cairo; Egypt; Department of Polymers and Pigments; National Research Center; Cairo; Egypt; Department of Pharmacology; Theodor Bilharz Research Institute; Giza; Egypt
    Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and its in vivo efficacy against Schistosoma mansoni were investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0-8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ. Copyright 2015, American Society for Microbiology. All Rights Reserved.