In-vitro toxicity evaluation of bismuth (iii) oxide particles synthesized using different reaction temperatures as promising radiographic contrast media / Nur Amirah Mohd Nor

Raise concern about the safety of current contrast media in patients with contraindications to iodinated media spur researchers to find safer options. Bismuth has gained attentions in the development of new contrast media for in-vivo imaging due to its high atomic number (Z = 83) which directly possess high X-ray attenuation coefficient, long circulation time in blood and cost effectiveness. However, this hypothetical application is hampered owing to challenges in synthesizing control for in vivo stability. This thesis aim to study in-vitro cytotoxicity of Bi2O3 particles synthesized hydrothermally using different reaction temperatures against iodinated contrast media. The cytotoxicity of Bi2O3 particles were assessed using human hepatocytes HeLa [Chang Liver] (ATCC CCL13™) and human embryonic hepatocytes WRL 68 (ATCC CL48™). Bi2O3 particles synthesized at 60, 90 and 120 °C were characterized using scanning electron microscope (SEM), transmission electron microscope (TEM) and zetasizer. The cytotoxicity of 100 μg/mL Bi2O3 particles in Chang liver and WRL 68 cells was measured using colorimetric cell viability (MTT) assay, intracellular reactive oxygen species (ROS) assay and mRNA expressions of endoplasmic reticulum (ER) stress genes, GRP 78 and CHOP. The characterization results revealed Bi2O3 particles synthesized at 60, 90 and 120 °C are rod-shaped with average diameter of 6.164, 6.703 and 7.010 μm, respectively. After 24 hours incubation, the cytotoxicity assays in both cell lines showed Bi2O3 particles has reduced cytotoxicity trend with higher reaction temperatures and bigger particles size. Chang liver cells are more susceptible to Bi2O3 particles cytotoxicity depicted with higher reduction of treated cells and high level of ROS while WRL 68 cells has higher resistant as only Bi2O3 particles synthesized at 60 °C was observed to be cytotoxic and all Bi2O3 particles induced low level of ROS. Bi2O3 particles showed acute cytotoxicity in both cell lines as the viability of treated cells increased with prolonged incubation time. Following to two different responses to cytotoxicity of Bi2O3 particles, GRP 78 and CHOP genes were expressed at low level in Chang liver cells to allow adaption for cell survival. Treated WRL 68 cells showed upregulations of GRP 78 and CHOP genes in decreasing cytotoxicity trend of Bi2O3 particles with higher reaction temperatures. In comparison to clinically-used iodine, Bi2O3 particles synthesized at 120 °C showed lower cytotoxic effect and suggest good biocompatibility as new contrast media.