Biapenem as a Novel Insight into Drug Repositioning against Particulate Matter-Induced Lung Injury

Abstract

The screening of biologically active chemical compound libraries can be an efficient way to reposition Food and Drug Adminstration (FDA)-approved drugs or to discover new therapies for human diseases. Particulate matter with an aerodynamic diameter equal to or less than 2.5 μm (PM2.5) is a form of air pollutant that causes significant lung damage when inhaled. This study illustrates drug repositioning with biapenem (BIPM) for the modulation of PM-induced lung injury. Biapenem was used for the treatment of severe infections. Mice were treated with BIPM via tail-vein injection after the intratracheal instillation of PM2.5. Alterations in the lung wet/dry weight, total protein/total cell count and lymphocyte count, inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were monitored in the PM2.5-treated mice. BIPM effectively reduced the pathological lung injury, lung wet/dry weight ratio, and hyperpermeability caused by PM2.5. Enhanced myeloperoxidase (MPO) activity by PM2.5 in the pulmonary tissue was inhibited by BIPM. Moreover, increased levels of inflammatory cytokines and total protein by PM2.5 in the BALF were also decreased by BIPM treatment. In addition, BIPM markedly suppressed PM2.5-induced increases in the number of lymphocytes in the BALF. Additionally, the activity of mammalian target of rapamycin (mTOR) was increased by BIPM. Administration of PM2.5 increased the expression levels of toll-like receptor 4 (TLR4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1, which were suppressed by BIPM. In conclusion, these findings indicate that BIPM has a critical anti-inflammatory effect due to its ability to regulate both the TLR4-MyD88 and mTOR-autophagy pathways, and may thus be a potential therapeutic agent against diesel PM2.5-induced pulmonary injury.

Sulforaphane Alleviates Particulate Matter-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells

“…In many previous studies, the effect of improving PM 2.5 -caused damage such as pulmonary injury, airway inflammation, and oxidative stress was analyzed in comparison with DEX. Thus, we have scrutinized the efficacy of SFN compared to DEX (33)(34)(35)(36). In the present study, SFN reversed PM 2.5 -induced cellular toxicity.…”

Biapenem Activity Against Meropenem-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa

“…Биапенем -это новый парентеральный антибактериальный агент с широким спектром антибактериальной активности in vitro, охватывающий многие грамотрицательные и грамположительные аэробные и анаэробные бактерии, включая штаммы, продуцирующие β-лактамазы [11].…”

Reactive Oxygen Species-Triggered Curcumin Release from Hollow Mesoporous Silica Nanoparticles for PM2.5-Induced Acute Lung Injury Treatment

“…Nowadays, the mainstream intervention is to use antiinflammatory drugs or antibiotics to interfere with the progression of pulmonary inflammation. 14,15 However, longterm use of anti-inflammatory drugs would induce severe side effects, including drug resistance and intestinal flora disturbance, which would limit their efficacy. 16 enhance the ability of loaded drugs to be specifically released at the site of disease, aiming to reducing damages to normal tissues.…”

“…Nowadays, the mainstream intervention is to use anti-inflammatory drugs or antibiotics to interfere with the progression of pulmonary inflammation. , However, long-term use of anti-inflammatory drugs would induce severe side effects, including drug resistance and intestinal flora disturbance, which would limit their efficacy . Recently, stimulus–response drug delivery systems (DDSs) have attracted great attention to enhance the ability of loaded drugs to be specifically released at the site of disease, aiming to reducing damages to normal tissues. , Among them, hollow mesoporous silica nanoparticles (HMSNs) are an ideal drug carrier due to their large surface area and unique high pore structure, which can effectively encapsulate different types of drugs. , In addition, the surface of HMSNs can be covered to achieve on-demand drug release as triggered by various stimuli, such as pH, redox potential, temperature, and ROS .…”