Metabolic effects of rosiglitazone and pioglitazone on Complex I and Complex II respiration in isolated rat mitochondria Public Deposited

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  • March 20, 2019
Creator
  • Braveboy-Wagner, Justin Steven
    • Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering
Abstract
  • Thiazolidinediones (TZDs) are believed to exert their antidiabetic effect through a variety of pathways and mechanisms, some of which relate to the toxic properties of these drugs. Research has proven that TZDs impair cell respiration in vitro and that they have an affect on oxidative stress within the cell. This paper investigates the role of mitochondria in rosiglitazone and pioglitazone action with respect to Complexes I and II of the respiratory chain. Inhibition of Complex I was confirmed via the reduced efficiency of mitochondrial respiration at increasing levels of drug concentration, with malate/glutamate as an energizing substrate, and in relation to Complex I (energized by succinate). Additionally, a decrease in the production of extra-mitochondrial reactive oxygen species (ROS) was detected, particularly on exposure to rosiglitazone, possibly correlating with a lower level of cytotoxicity in comparison to pioglitazone.
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  • In Copyright
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  • "... in partial fulfillment of the requirements for the degree of Master of Science in Biomedical Engineering Chapel Hill, North Carolina."
Advisor
  • Macdonald, Jeffrey
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  • Chapel Hill, NC
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  • Open access
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