Acetamiprid-induced pulmonary toxicity via oxidative stress, epithelial-mesenchymal transition, apoptosis, and extracellular matrix accumulation in human lung epithelial cells and fibroblasts: Protective role of heat-killed Lactobacilli.

Abstract

Acetamiprid (ACE) is a neonicotinoid insecticide with widespread global application, resulting in persistent human exposure. The current research examined the toxicological implications of ACE exposure on human lung fibroblasts (MRC-5 cells) and bronchial epithelial cells (BEAS-2B cells). The following implications were explored: oxidative stress, epithelial-mesenchymal transition, apoptosis, cellular proliferation, and extracellular matrix accumulation. The prospective protective properties of heat-killed Lactobacillus fermentum and Lactobacillus delbrueckii (HKL) were further studied. The 14-day exposure to ACE at 4 μM triggered oxidative stress and inflammation. ACE promoted epithelial-mesenchymal transition, as evidenced by the decline of protein and mRNA abundances of E-cadherin alongside increased protein and mRNA quantities of α-SMA and N-cadherin in BEAS-2B cells. Additionally, it elicited apoptosis in BEAS-2B cells and stimulated the cellular growth of MRC-5 cells. The TGF-β1/ Smad pathway was activated upon ACE exposure, leading to the accumulation of extracellular matrix. HKL demonstrated antioxidant, anti-apoptotic, anti-proliferative, and anti-fibrotic properties, mitigating ACE-induced toxicity. Our findings delineate the molecular mechanisms underlying epithelial-mesenchymal transition, inflammation, oxidative stress, and extracellular matrix accumulation in ACE-induced pulmonary fibrosis, which provides new insights into pulmonary injury. Additionally, this investigation would offer us an approach to mitigate lung deterioration induced by ACE through utilizing heat-killed probiotic supplementation.