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The Cellular and Molecular Mechanism of Third Hand Cigarette Smoke-Induced Hepatic Steatosis

  • Author(s): Flores, Cristina
  • Advisor(s): Martins-Green, Manuela
  • et al.
Creative Commons 'BY-NC-ND' version 4.0 license

Recent evidence indicates that third hand smoke (THS) is present mainly in places where smoking happens regularly but also in places where smoking has been banned but previously happened regularly. THS toxins remain in the contaminated surfaces, are re-emitted and have the ability to react with atmospheric gases to produce dangerous carcinogenic compounds. New evidence regarding the toxicity of THS continues to emerge and has been accumulating for the past 5 years. In order to investigate effects of THS toxins in the liver, I took a molecular and cellular approach by performing multiple cellular assays to study important cellular processes involved in lipid metabolism. The rodent model I used mimics human chronic exposure to THS and separates the effects of SHS (second hand smoke) from THS. I also used different drug treatments and antioxidant treatments to modulate the effects of THS in mice and determine whether oxidative stress plays a key role in the development of THS-induced hepatic steatosis. Using this cellular and molecular approach, I was able to show that THS toxins alter the oxidative stress levels and increase oxidative-stress-mediated damage (protein damage, DNA damage and functional damage) in mice resulting in abnormal lipid metabolism. I was also able to show regulatory pathways, which involve regulators such as AMPK, SIRT1 and SREBP1c, are altered by THS toxins.

Furthermore, THS toxins alter fatty acid metabolism and lead to a decrease in VLDL assembly contributing to accumulation of lipids in the liver. THS-exposed mice have high levels of TG and fatty acids and less ATP production, suggesting these animals are less efficient metabolically compared to the control mice. AICAR treatment resulted in a decrease of fatty acids and TG levels, suggesting that increasing Suirtin 3 (SIRT3), a key regulator of fatty acid metabolism results in less lipid accumulation in the liver. These findings provide evidence of the cellular and molecular basis of THS-induced hepatic steatosis in mice.

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