Comparative toxicity profile of a heated-tobacco product and cigarette smoke extract in human hepatocellular carcinoma cells

Reıs R. , Kolci K., Sipahi H.

13th ÖGMBT Annual Meeting "From Molecular Machines to Translational Medicine", Innsbruck, Austria, 20 September - 14 October 2021, pp.138

  • Publication Type: Conference Paper / Summary Text
  • City: Innsbruck
  • Country: Austria
  • Page Numbers: pp.138


The ‘heated tobacco product’ (HTP) was marketed as a brand-new technology introduced by tobacco companies with reduced toxicity compared to conventional cigarettes. Although HTPs are marketed as an “alternative” to cigarettes regarding their diminished burned-byproducts, it is still uncertain to define their long-term effects as well as their other target organ toxicities. Recent findings demonstrated that smoking is associated with NAFLD, thus might be a contributing risk factor for liver disease progression. In the present study, we aimed to identify the comparative toxicological profile of an HTP and cigarette smoke extract (CSE) through oxidative and inflammatory response in HepG2 cells. In addition, a popular hepatoprotective agent alpha-lipoic acid (α-LA) has been tested against CSE/HTP- induced toxicity. For this purpose, HepG2 cells were treated with CSE and HTP extracts containing approximate amounts of nicotine, for 24 h whereas α-LA was used for 4 h prior to CSE/HTP exposure. According to the results, both HTP and CSE led to a dose-dependent decline in cell viability, prominently with CSE. Oxidative damage and lipid peroxidation were significantly induced by CSE in HepG2 cells through an increase in MDA level, CAT and SOD activity, and GSH depletion, whereas HTP slightly increased MDA level and GSH depletion (p<0.05). In addition, ALT and AST enzymatic activity remarkably up-regulated in the CSE group (p<0.01), while HTP exposure resulted in a slight increase. The α-LA pre-treatment has also reversed the CSE/ HTP toxicity through oxidative damage and liver dysfunction. In addition, the inflammatory response by NO and IL-6 release was increased by CSE whereas HTP did not alter inflammatory parameters significantly. Furthermore, the free AhR level, a transcription factor mediating toxicity, inflammatory response, and metabolism, was down-regulated by both CSE and HTP, which might be due to AhR activation through its nuclear translocation, which was notable with CSE owing to its AhR-ligand content. According to the results, it was seen that CSE has more deleterious effects on oxidative and inflammatory response than that of HTP in the liver in vitro. Even though HTPs are claimed to be ‘harmless’, these products might contribute tobacco-induced liver disease progression in chronic exposure and should not be replaced with cigarettes to quit smoking since its long-term side-effects are undefined.