Effects of heated tobacco vapor, nicotine, and cigarette smoke exposures on C. elegans neuroimmune interactions and host defense

• Grant number: 22/14025-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 13, 2023
• End date: March 12, 2024
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Sandra Helena Poliselli Farsky
• Grantee: Pablo Rhansan dos Santos Scharf
• Supervisor: Michael Aschner
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Albert Einstein College of Medicine, United States
• Associated to the scholarship: 20/14368-3 - EFFECTS OF THE EXPOSURE TO TOBACCO PRODUCTS ON CD4 + T LYMPHOCYTES INVOLVED IN THE GENESIS OF MULTIPLE SCLEROSIS, BP.DR

Abstract

Heated tobacco products (HTP) are non-combustible devices that release nicotine, humectants, and lower combustible xenobiotics than cigarette smoke (CS), emerging as a potential harm reduction tool for current smokers. CS and nicotine are known to impair host defense by altering the immune system response; however, further investigations are required to evaluate the immunotoxicity of HTP. C. elegans is a powerful tool routinely used in the neuroscience, since its nervous system shares several features with mammals. C. elegans defense is orchestrated by multiple neural interactions that enable behavioral changes and inflammatory-like responses to sense and avoid pathogens or fight against infections to survive. Since C. elegans shares conserved pathways related to hosting defense, these animals emerge as a potential platform to evaluate the impact of potentially harmful products on innate inflammatory responses. As toxic effects and mechanisms related to HTP exposures claims for scientific approaches for the proposal of a harm reduction agent,,Herein, we aim to investigate the effects of HTP, nicotine, and CS on the neuroimmune interactions related to C. elegans host defenses pathways and behaviors. Wild-type N2 strains will be exposed to CS or HTP using a peristaltic pump system, and nicotine will be diluted in the nematode culture. The exposure protocol cycle will be determined using nematode viability and oxidative stress responses as parameters. Exposed animals will be challenged with pathogenic bacteria to evaluate their avoidance behavior and survival. RNA sequencing will be performed to identify the altered pathways in exposed animals. The data obtained here will allow the evaluation of HTP, CS, and nicotine effects on neuroimmune functions and their impact on the host defenses. Moreover, the characterization of alternative and cheaper experimental models otherwise than mammals is required to evaluate risk assessment and to corroborate mechanisms of toxicity. (AU)