L-carnosine Attenuates Bleomycin-Induced Oxidative Stress via NFκB Pathway in the Pathogenesis of Pulmonary Fibrosis

Abstract

Idiopathic Pulmonary fibrosis (IPF), a chronic interstitial lung disease, has pulmonary manifestations clinically characterized by collagen deposition, epithelial cell injury, and a decline in lung function. L-carnosine, a dipeptide consisting of β-alanine and L-histidine, has demonstrated a therapeutic effect on various diseases because of its pivotal function. Despite the effect of L-carnosine in experimental IPF mice, its anti-oxidative effect and associated intercellular pathway, particularly alveolar epithelial cells, remain unknown. Therefore, we demonstrated the anti-fibrotic and anti-inflammatory effects of L-carnosine via Reactive oxygen species (ROS) regulation in bleomycin (BLM)-induced IPF mice. The mice were intratracheally injected with BLM (3 mg/kg) and L-carnosine (150 mg/kg) was orally administrated for 2 weeks. BLM exposure increased the protein level of Nox2, Nox4, p53, and Caspase-3, whereas L-carnosine treatment suppressed the protein level of Nox2, Nox4, p53, and Caspase-3 cleavage in mice. In addition, the total SOD activity and mRNA level of Sod2, catalase, and Nqo1 increased in mice treated with L-carnosine. At the cellular level, a human fibroblast (MRC-5) and mouse alveolar epithelial cell (MLE-12) were exposed to TGFβ1 following L-carnosine treatment to induce fibrogenesis. Moreover, MLE-12 cells were exposed to cigarette smoke extract (CSE). Consequently, L-carnosine treatment ameliorated fibrogenesis in fibroblasts and alveolar epithelial cells, and inflammation induced by ROS and CSE exposure was ameliorated. These results were associated with the inhibition of the NFκB pathway. Collectively, our data indicate that L-carnosine induces anti-inflammatory and anti-fibrotic effects on alveolar epithelial cells against the pathogenesis of IPF.

TMT proteomics analysis reveals the mechanism of bleomycin-induced pulmonary fibrosis and effects of Ginseng honeysuckle superfine powdered tea

“…PF is characterized by abnormal proliferation and apoptosis of fibroblasts and excessive accumulation of extracellular matrix. Many varieties of factors can trigger pulmonary fibrosis, such as viral and bacterial infection, cigarette exposure, and environmental particles [ 2 ]. There is growing evidence to support the link between PF, oxidative stress, epithelial-to-mesenchymal transition (EMT), and ferroptosis [ 3 , 4 ].…”