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ORIGINAL RESEARCH article
Front. Toxicol.
Sec. Environmental Toxicology
Volume 6 - 2024 |
doi: 10.3389/ftox.2024.1515850
Heat-not-burn technology affects plasma testosterone levels and markers of inflammation, oxidative stress in the testes of rats
Provisionally accepted
Silvia Granata
1
Camilla Morosini
1
Mariachiara Valerii
2
Ivan Fagiolino
3
Stefano Sangiorgi
1
Severino Ghini
1
Enzo Spisni
2*
Fabio Vivarelli
1*
Lucy C Fairclough
4
Moreno Paolini
1
Donatella Canistro
1- 1 Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- 2 Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Emilia-Romagna, Italy
- 3 Gruppo CSA—S.p.A, Rimini, Italy
- 4 School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, England, United Kingdom
Heating tobacco products (HTPs) are advanced electronic cigarette models. classified by the FDA as a modifiedrisk tobacco product and can be used as part of efforts to quit smoking. Using heat-not-burn (HnB) technology, these devices heat tobacco avoiding complete combustion. Although the levels of toxicants in the mainstream are significantly lower than those observed in tobacco smoke, some recent studies have raised concerns about potential health risks associated with their use, particularly regarding their effects on male gonadal function, which remain largely unexplored. Here, we show in a 4-week rodent whole-body exposure model to tobacco HnB on adult male Sprague Dawley rats, that the expression of the cell cycle regulators Bax/Bcl-2 ratio is not affected, along with no changes in p-38 . On the other hand, an increase in oxidative stress markers, including those associated with DNA damage, was observed in exposed animals, along with the induction of NF-kB dependent pro-inflammatory mediators: TNF-α, IL-1β, IL-6 and COX-2. Furthermore, inactivation of key androgenic enzymes, such as 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, together with decreased testosterone synthesis suggest a potential impairment of male gonadal function. The results indicate that animals exposed to HnB smoke show higher levels of oxidative stress markers, including those associated with DNA damage, as well as higher levels of pro-inflammatory cytokines. The impairment of some androgenic key enzymes and those related to the activity of seminiferous epithelium, together with the decrease in testosterone levels, suggest an impairment of gonadal function through the alteration of some cellular pathways typically associated with tobacco consumption.
Keywords: Heat-not-Burn, Oxidative Stress, Inflammation, DNA Damage, Testis
Received: 23 Oct 2024; Accepted: 31 Dec 2024.
Copyright: © 2024 Granata, Morosini, Valerii, Fagiolino, Sangiorgi, Ghini, Spisni, Vivarelli, Fairclough, Paolini and Canistro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Enzo Spisni, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, 40126, Emilia-Romagna, Italy
Fabio Vivarelli, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
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