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Effects of the hot not burn tobacco exposure on rheumatoid arthritis

Grant number: 19/19573-7
Support type:Regular Research Grants
Duration: May 01, 2020 - April 30, 2022
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal researcher:Sandra Helena Poliselli Farsky
Grantee:Sandra Helena Poliselli Farsky
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Mauricio Yonamine

Abstract

The incidence of rheumatoid arthritis (RA) is increasing worldwide, which leads to public health concerns, as the disease causes chronic and severe morbidity, there are no effective treatments, and existing ones, such as biological drugs, are high cost. The genesis of RA has a genetic and environmental basis, and in this last context, exposure to tobacco stands out. Because of the recognized harm of tobacco exposure to human health, some strategies have been developed on an industrial scale to reduce exposure to the many toxic compounds of tobacco combustion. Among the products developed is IQOS (I Quit Ordinary Smoking), developed by Philip Morris International ", based on heat-not-burn technology, which leads to the heating of nicotine-containing tobacco, potentially reducing the release of combustion products. In the present project we aim to evaluate the effects of IQOS on RA and the toxicity mechanisms responsible for the observed effects. To this proposal, RA will be induced in male DBA1 / J mice by injection of collagen of chicken into the base tail, and the animals will be exposed during the last seven days of disease to the heated tobacco vapor (iQOS), conventional cigarette and fresh air in exposure chambers simultaneously. Animals exposed to cigarette and IQOS will receive the same nicotine concentration. At the end of the experiments (35 days after RA induction), the animals will be analyzed for the clinical parameters of the disease and the following biological samples will be collected: 1) blood for total and differential leukogram and for quantitation of nicotine, cotinine and carboxyhemoglobin; 2) synovial fluid and synovial membrane for histological, biochemical and molecular biology studies to characterize inflammation; 3) lymph node and spleen samples for characterization of leukocyte subtypes; 4) lung and liver samples for quantification of proteins involved in RA. In addition, primary lymphocytes collected from spleen of mice or human synovocytes will be in vitro exposed to IQOS, cigarette and air in cell exposure chambers. In lymphocytes the effects of exposures on Th17 and Treg lymphocyte proliferation and polarization will be investigated, as Th17/Treg balance is a mechanism described for the genesis of RA on cigarette exposure; in the synoviocytes, inflammatory and oxidative stress parameters will be evaluated. It is noteworthy the project's originality, especially in Brazil, and that the in vivo and in vitro exposure systems employed are unique in Brazil, and they were assembled by our research group with all the controls required for the controlled exposures. Thus, the results obtained will be fundamental to clarify the potential of heated tobacco vapor in reducing the risk of tobacco exposure. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
HELUANY, CINTIA SCUCUGLIA; DONATE, PAULA BARBIM; SCHNEIDER, AYDA HENRIQUES; FABRIS, ANDRE LUIS; GOMES, RENAN AUGUSTO; VILLAS-BOAS, ISADORA MARIA; TAMBOURGI, DENISE VILARINHO; DA SILVA, TARCILIA APARECIDA; TROSSINI, GUSTAVO HENRIQUE GOULART; NALESSO, GIOVANNA; SILVEIRA, EDUARDO LANI VOLPE; CUNHA, FERNANDO QUEIROZ; FARSKY, SANDRA HELENA POLISELLI. Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways. ANTIOXIDANTS, v. 10, n. 6 JUN 2021. Web of Science Citations: 0.
SCHARF, PABLO; DA ROCHA, GUSTAVO H. O.; SANDRI, SILVANA; HELUANY, CINTIA S.; PEDREIRA FILHO, WALTER R.; FARSKY, SANDRA H. P. Immunotoxic mechanisms of cigarette smoke and heat-not-burn tobacco vapor on Jurkat T cell functions. Environmental Pollution, v. 268, n. B JAN 1 2021. Web of Science Citations: 0.
SCHARF, PABLO; BROERING, MILENA FRONZA; OLIVEIRA DA ROCHA, GUSTAVO HENRIQUE; FARSKY, SANDRA HELENA POLISELLI. Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 19 OCT 2020. Web of Science Citations: 0.

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