Toxic mechanisms of tobacco products under neutrophil production and mobilized in normal conditions and in rheumatoid arthritis

• Grant number: 22/11779-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• Status: Discontinued
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Sandra Helena Poliselli Farsky
• Grantee: Pâmela Pacassa Borges
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/12040-1 - Smoking Influence on Neutrophils During Fracture and Tissue Recovery, BE.EP.DR

Abstract

Smoking is a chronic disease triggered by nicotine dependence, besides the numerous toxic compounds released from tobacco combustion. Thus, forms of exposure to nicotine have been developed, including the Heat Not Burn Tobacco (HNBT), which consists of exposure by heating tobacco, without generating combustion. Although it is proposed that HNBTs may be less toxic than conventional cigarettes (CC), there are not enough data to assess their risk. Data from our group show that exposure of mice to HNBT impairs the mobilization of neutrophils to the inflamed compartment in the presence of rheumatoid arthritis (RA). Thus, this project will investigate the effect of exposure to CC, HNBT or aerosolized nicotine on the mechanisms of production and mobilization of neutrophils from the bone marrow to the blood, and from this to the tissues under normal conditions or in the presence of antigen-induced RA ( AIA). Exposures to CC, HNBT, or air (control) in vivo will occur following the Canadian exposure regime, in daily exposures (2 times a day, 1 hour each), for 5 days, according to protocols already established in the laboratory. Exposures in RA animals will be performed from days 16 to 20 after antigen sensitization, on day 21, animals will be challenged with antigen, and samples will be collected 24 hours later. Nicotine exposures will be performed in the same manner as the protocol described above. The following samples will be collected: peripheral blood and bone marrow perfusate for total and differential leukocyte count and immunophenotyping; plasma and synovial lavage to measure inflammatory mediators; lymphoid organs for immunophenotyping; whole blood for measurement of serum levels of nicotine, cotinine, polycyclic aromatic hydrocarbons, carbonyl compounds and carboxyhemoglobin. In vitro assays will be performed, using the C1498 strain (murine lymphoblasts) to evaluate mechanisms of cytotoxicity that may be involved in the impairment of granulopoiesis. The project proposed here is unprecedented and the results obtained will elucidate mechanisms of toxicity caused by different products involved in smoking.

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)

FERREIRA, LUIZ PHILIPE DE SOUZA; DA SILVA, RAFAEL ANDRE; BORGES, PAMELA PACASSA; XAVIER, LUANA FILIPPI; SCHARF, PABLO; SANDRI, SILVANA; OLIANI, SONIA M.; FARSKY, SANDRA H. P.; GIL, CRISTIANE D.. Annexin A1 in neurological disorders: Neuroprotection and glial modulation. PHARMACOLOGY & THERAPEUTICS, v. 267, p. 10-pg., 2025-03-01. (22/11779-8, 22/12027-0, 21/00270-4, 22/02327-6, 22/14025-4)

SCHARF, PABLO; SANDRI, SILVANA; BORGES, PAMELA PACASSA; DE OLIVEIRA, TIAGO FRANCO; FARSKY, SANDRA HELENA POLISELLI. A single and short exposure to heated tobacco vapor or cigarette smoke affects macrophage activation and polarization. Toxicology, v. 506, p. 5-pg., 2024-06-14. (20/14368-3, 19/19573-7, 22/11779-8)