Basic Informations

C.V

PROFESSIONAL EXPERIENCE

Master Title

Pharmacological study of the possible interactions between certain analgesics and some antioxidants in experimental animals

Master Abstract

The present work was conducted to study the possible protective actions of some antioxidants, namely zinc, selenium, vitamin E and Ginkgo biloba extract against diclofenac sodium-induced gastric ulcer compared to ranitidine as a reference anti-ulcer agent on acute and 14 days daily treatment. The possible anti-inflammatory actions of the chosen antioxidants and their possible interactions with diclofenac sodium on acute and 7 days daily treatment were also studied. In the present study, two different models of animal experiments have been involved. The first was rat pyloric ligation model. It was constructed to evaluate the possible anti-ulcer effects of the chosen antioxidants against diclofenac-induced gastric ulcer on acute and 14 days daily treatment. The anti-ulcerogenic potentials of the test drugs were evaluated based on number of ulcers, ulcer index, gastric volume, titratable acidity, peptic activity, mucin concentration and gastric mucosal content of histamine and glutathione. Pyloric ligation was performed in order to collect suitable volumes of the gastric juice. The chosen doses for acute treatment in pyloric ligation model were; diclofenac sodium (60 mg/kg), ranitidine (150 mg/kg), zinc sulphate (80 mg/kg), sodium selenite (2.3 mg/kg), vitamin E (100 mg/kg) and Ginkgo biloba extract (100 mg/kg). For 14 days daily treatment, the chosen doses were; diclofenac sodium (10 mg/kg), ranitidine (100 mg/kg), zinc sulphate (50 mg/kg), sodium selenite (0.3 mg/kg), vitamin E (100 mg/kg) and Ginkgo biloba extract (100 mg/kg). All the test drugs and ranitidine were administered by oral feeding tube while diclofenac sodium was administered by intraperitoneal injection. The second model of experiments was carrageenan-induced granuloma pouch in rats. It was conducted to evaluate the possible anti-inflammatory actions of the chosen antioxidants and their interactions with diclofenac sodium on both acute and 7 days daily treatment. The anti-inflammatory potentials of the test drugs were evaluated based on exudate volume and exudate content of histamine, protein and total leukocyte. The chosen doses for acute treatment in carrageenan-induced granuloma pouch model were; diclofenac sodium (25 mg/kg), zinc sulphate (25 mg/kg), sodium selenite (2.3 mg/kg), vitamin E (100 mg/kg) and Ginkgo biloba extract (100 mg/kg). For 7 days daily treatment, the chosen doses were; diclofenac sodium (5 mg/kg), zinc sulphate (5 mg/kg), sodium selenite (0.2 mg/kg), vitamin E (100 mg/kg) and Ginkgo biloba extract (100 mg/kg). All the test drugs and ranitidine were administered by oral feeding tube while diclofenac sodium was administered by intraperitoneal injection.

PHD Title

Molecular Pharmacology and Preclinical Studies of Novel Small-Molecule Targeted agents for the Treatment of Hepatocellular Carcinoma

PHD Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and Africa, which is lethal in about 75% of cases. In the United States, there are 6,000-9,000 new cases of HCC per year. HCC is one of the highly chemo-resistant cancers, for which systemic treatments have been unsuccessful. The available therapies are surgical (10-20% of cases), locoregional or recently, chemical using Sorafenib, a multi-kinase inhibitor which has been shown in clinical trial to add two months to the lifespan of late stage HCC patients. To combat HCC with its assortment of genomic and cellular aberrations that occur during the progression of the disease, we have developed OSU-A9 and OSU-2S, novel small-molecule targeted agents for HCC therapy, using indole-3-carbinol (I3C) and fingolimod (FTY720) respectively, as scaffolds. In this study, we used pharmacological and molecular genetic approaches to investigate the mechanisms of action of the lead compounds of these classes (OSU-A9 and OSU-2S) and assess both the efficacy and safety in a series of preclinical studies carried out both in vitro and in vivo.