Peer-Reviewed Publications

    Impact of aerosols on liver xenobiotic metabolism: A comparison of two methods of exposure

    Bovard, D.; Renggli, K.; Marescotti, D.; Sandoz, A.; Majeed, S.; Pinard, L.; Ferreira, S.; Pak, C.; Barbier, A.; Beguin, A.; Iskandar, A.; Frentzel, S.; Hoeng, J.; Peitsch, M. C.

    Published
    Nov 27, 2021
    DOI
    10.1016/j.tiv.2021.105277
    PMID
    34843886
    Link to publication
    Topic
    Summary

    Assessment of aerosols effects on liver CYP function generally involves aqueous fractions (AF). Although easy and efficient, this method has not been optimized recently or comparatively assessed against other aerosol exposure methods. Here, we comparatively evaluated the effects of the AFs of cigarette smoke (CS) and Tobacco Heating System (THS) aerosols on CYP activity in liver spheroids. We then used these data to develop a physiological aerosol exposure system combining a multi-organs-on-a-chip, 3D lung tissues, liver spheroids, and a direct aerosol exposure system. Liver spheroids incubated with CS AF showed a dose-dependent increase in CYP1A1/1B1, CYP1A2, and CYP2B6 activity and a dose-dependent decrease in CYP2C9, CYP2D6, and CYP3A4 activity relative to untreated tissues. In our physiological exposure system, repeated CS exposure of the bronchial tissues also caused CYP1A1/1B1 and CYP1A2 induction in the bronchial tissues and liver spheroids; but the spheroids showed an increase in CYP3A4 activity and no effect on CYP2C9 or CYP2D6 activity relative to air-exposed tissues, which resembles the results reported in smokers. THS aerosol did not affect CYP activity in bronchial or liver tissues, even at 4 times higher concentrations than CS. In conclusion, our system allows us to physiologically test the effects of CS or other aerosols on lung and liver tissues cultured in the same chip circuit, thus delivering more in vivo like data.

    Related Publications

    A comparative assessment of HPHC yields and in vitro toxicity for 1R6F reference cigarette smoke versus aerosol generated by Tobacco Heating System 3.0

    Pre-clinical Toxicology

    Cigarette smoke enhances abdominal aortic aneurysm formation in angiotensin II-treated apolipoprotein E-deficient mice

    Pre-clinical Toxicology

    Tobacco Heating System 2.4 has less harmful impact on 2D bone co-culture system than cigarette smoke

    Pre-clinical Toxicology

    Characterizing the Genotoxic Potential of E-Cigarette Components In Vitro

    Pre-clinical Toxicology

    Evaluation of Chronic Toxicity and Carcinogenicity of Flavored E-Vapor Aerosols in an 18-Month Inhalation Study in A/J Mice

    Pre-clinical Toxicology

    Toxicological Assessment of Highly Mentholated Reduced-Risk Tobacco Products in Sprague Dawley Rats Following Sub-Chronic Inhalation Exposure

    Pre-clinical Toxicology

    PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
    ​
    Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.