Title: Protective effects of nicotine with or without PPAR-γ inhibition in saline lavage-induced lung injury in rats.

Activation of α7nAChRs and PPAR-γ exerts anti-inflammatory effects, and evidence suggests a potential interaction between these pathways. This study investigated their interaction in a saline lavage-induced model of acute respiratory distress syndrome (ARDS). Fifty male Sprague-Dawley rats were assigned to five groups: SHAM, lavage-induced ARDS (LAV), LAV treated with nicotine (NIC), LAV treated with the PPAR-γ antagonist bisphenol A diglycidyl ether (BAG), and LAV treated with both BAG and NIC. Hemodynamic parameters, arterial blood gases, bronchoalveolar lavage fluid (BALF) polymorphonuclear neutrophil (PMN) counts, blood neutrophil-to-lymphocyte ratio (NLR), lung wet-to-body weight ratio (LW/BW), plasma nitric oxide metabolites (NOx), lung elastance, vital capacity (VC), and total lung capacity (TLC) were evaluated. Saline lavage induced severe lung injury, characterized by impaired gas exchange, increased lung elastance, reduced VC and TLC, elevated BALF PMN counts, increased LW/BW, and elevated plasma NOx levels. Nicotine significantly improved hemodynamic parameters, gas exchange, and lung mechanics while reducing BALF PMN counts, LW/BW ratio, and plasma NOx levels. PPAR-γ inhibition attenuated several of these protective effects, including improvements in gas exchange, inflammatory indices (BALF PMN count and blood NLR), plasma NOx levels, and hemodynamic parameters. However, nicotine retained partial efficacy in the presence of BAG. Collectively, nicotine attenuated pulmonary inflammation and improved lung function in experimental ARDS. The attenuation of these protective effects by PPAR-γ inhibition suggests that PPAR-γ signaling may contribute to the protective actions of nicotine, potentially in interaction with α7nAChR-dependent pathways.