The Cytotoxic Effects of Methylmercury on Cardiomyocytes: A Possible Implication for Heart Diseases?
|Title:||The Cytotoxic Effects of Methylmercury on Cardiomyocytes: A Possible Implication for Heart Diseases?|
|Abstract:||Methylmercury (MeHg) is known predominantly as a neurotoxicant, however emerging experimental and epidemiological evidence has shown associations between MeHg exposure and the potential for increased risks of cardiovascular diseases. This thesis investigated the in vitro cytotoxic effects of MeHg in two cardiomyocyte cell lines, H9C2 rat neonatal cell line and AC16 adult human cell line. We observed significant increases in cell death at concentrations from 1 – 10 µM. ROS production and intracellular calcium concentrations increased dose-dependantly with MeHgCl exposure. Furthermore, while assessing mitochondrial function, a decline in maximal respiration at 1 µM was seen. However, these observations may in turn be a direct consequence of decreased cell numbers following exposures. Additionally, this study highlighted the differences in cellular bioenergetics which may impact how certain cells respond to contaminant stressors. The distribution of MeHg and total Hg in rat heart tissues was also examined and we observed increasing concentrations of MeHg in high and low dosed rat groups as compared to the vehicle controls. No difference was observed in Hg levels between the normal and high fat and sugar diet groups. The urinary isoprostane levels, which are indicative of systemic oxidative stress, showed significant increases in lean rats exposed to the high dose treatment. It was also observed that a high fat and sugar diet in lean and obese rats can contribute to increasing oxidative stress regardless of the level of contaminants they were dosed with. This thesis demonstrated several in vitro effects of MeHg on heart cells as well as determine the distribution of Hg levels in heart tissues and oxidative stress markers from an in vivo study.|
|Collection||Thèses, 2011 - // Theses, 2011 -|