Master of Science in Pharmaceutical Sciences, University of Toledo, 2010, Pharmaceutical Science

Ambroxol is an active metabolite of bromexine that has been proven to possess a great bronchosecretolytic effect and has been used to treat infants from 0 to 6 month and children till over 12 years of age, as well as adults. My thesis research was aimed to detect potential adverse effects of ambroxol on development using zebrafish embryos/larvae as a model and to investigate the possible involvement of the zebrafish cytosolic sulfotransferases (SULTs) in the protection against the possible adverse effects. Developing eggs at 24 hpf, 48 hpf, and 72 hpf were exposed to different concentrations (1mM, 0.5 mM, 0.25 mM, 0.125 mM, and 0.05 mM) of ambroxol in triplicate and observations were made daily for eleven consecutive days. Ambroxol induced cardiac edema and bradycardia at different stages of development in a dose-dependent manner. Enzymatic assay of purified zebrafish SULTs showed significant sulfation of ambroxol by SULT2 ST1 and SULT3 ST1, 2, 3, 4, and 5. How these SULTs may be involved in protection against the adverse effects of ambroxol remains to be clarified.

Committee: Ming-Cheh Liu PhD (Committee Chair); Frederick Williams PhD (Committee Member); Zahoor Shah PhD (Committee Member) Subjects: Pharmacology

MS, University of Cincinnati, 2003, Medicine : Environmental Health Sciences

PBBs are known to cause negative health effects in humans and in animals. It is unknown if these effects are mediated by an underlying genetic component of the AHR phenotype. In this study, we examined the developmental effects of both coplanar and noncoplanar PBBs on mouse lines having both high and low affinity AHR phenotype with C57BL/6J background. We determined a coplanar PBB high-affinity AHR-dependent neonatal lethality and immunotoxicity, coupled with the induction of CYP1A1 in embryonic liver and brain at gestational day 18.

Committee: Dr. Daniel W. Nebert (Advisor) Subjects: Health Sciences, Toxicology

Doctor of Philosophy, The Ohio State University, 2012, Chemical and Biomolecular Engineering

Drug screening is a long and costly process confronted with low productivity and challenges in using animals. 3-D cell-based high-throughput platforms have been developed to improve drug-screening efficiency and minimize animal testing. However, online monitoring of cell proliferation, pH, and dissolved oxygen (DO) has been a challenge in 3-D cell-based assays. In this work, a 40 micro-well plate bioreactor (40-MBR) system was developed as a high-throughput platform for 3-D cell cultures. This 40-MBR has similar dimensions of a 384-well plate (384-MWP) can provide real-time and noninvasive monitoring of cell proliferation, pH, and DO in 3-D microenvironments. A colon cancer cell line expressing enhanced green fluorescent protein (EGFP) under the control of a constitutive CMV promoter was tested with two potential cancer drugs using the 40-MBR and 384-MWP. Compared to the 384-MWP, the 40-MBR gave more reliable and highly reproducible growth kinetic data with reduced experimental errors. This study demonstrated the potential application of the 40-MBR as a high-throughput platform for screening potential cancer drugs and evaluating their cytotoxic effects in the early-stage drug discovery. Cytotoxicity and embryotoxicity of chemicals were also investigated in the 40-MBR using EGFP-expressing embryonic stem cells (ESCs). Embryonic stem cell test (EST) has been used as an in vitro model for assessing embryotoxicity. However, the current EST can only provide end-point data and cannot predict embryotoxicity of chemicals affecting organs such as bone. In this study, a novel high-throughput embryotoxicity assay was developed using EGFP-expressing ESCs under the control of a survivin promoter. Survivin expression is closely associated with embryo development and cell differentiation. For control, ESCs expressing EGFP under the control of a CMV promoter were used to monitor cytotoxicity of chemicals. Using survivin as a diagnostic marker for predicting embryotoxicity was fi (open full item for complete abstract)

Committee: Shang-Tian Yang (Advisor); Jeffery Chalmers (Committee Member); Andre Palmer (Committee Member) Subjects: Chemical Engineering