Preventive Effects of Valnemulin on Lipopolysaccharide-Induced Acute Lung Injury in Mice

Abstract

Valnemulin reportedly regulates inflammatory responses in addition to its in vitro antibacterial activity. In this study, we established a mouse model of lipopolysaccharide (LPS)-induced inflammatory lung injury and investigated the effect of valnemulin (100 mg/kg) on acute lung injury (ALI) 8 h after LPS challenge. We prepared bronchoalveolar lavage fluid (BALF) for measuring protein concentrations, cytokine levels, and superoxidase dismutase (SOD) activity, and collected lungs for assaying wet-to-dry weight (W/D) ratios, myeloperoxidase (MPO) activity, cytokine mRNA expression, and histological change. We found that the pre-administration of valnemulin significantly decreases the W/D ratio of lungs, protein concentrations, and the number of total cells, neutrophils, macrophages, and leukomonocytes, and histologic analysis indicates that valnemulin significantly attenuates tissue injury. Furthermore, valnemulin significantly increases LPS-induced SOD activity in BALF and decreases lung MPO activity as well. In addition, valnemulin also inhibits the production of tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta, which is consistent with mRNA expression in lung. The results showed that valnemulin had a protective effect on LPS-induced ALI in mice.

Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery

“…These are the primary multifunctional cytokines produced from inflammatory cells that exacerbate the extent of lung injury [41]. As in previous studies [42,43], our results showed that the expressions of TNF-α, IL-6 and IL-1ß were significantly increased in BAL fluid after LPS administration as compared to control group, whereas administration of imatinib or nilotinib significantly downregulated the expression of these cytokines as compared to the LPS group.…”

The Effects of the Combination of Sodium Ferulate and Oxymatrine on Lipopolysaccharide-Induced Acute Lung Injury in Mice

“…Despite recent advances in critical care and significant efforts invested in the basic research and clinical trials of ALI, its mortality rate (35%-45%) had remained relatively unchanged since [2]. The inflammatory process played a key role in the development of ALI, and the main pathological change of ALI was acute leakage inflammatory response with leakage of protein into the alveolar space, inflammatory cells accumulation, interstitial edema, and disruption of epithelial integrity [3]. Therefore, it was significant that anti-inflammatory drugs were used to reduce lung injury at early stage of ALI.…”

Antibacterial Activity and Pharmacokinetic Profile of a Promising Antibacterial Agent: 22-(2-Amino-phenylsulfanyl)-22-Deoxypleuromutilin

“…Some antibacterial agents not only could regulate immune and inflammatory responses but also possessed antibacterial activity [23]. Valnemulin was proved to have effect on the inflammatory responses for the treatment of LPS-induced acute lung injury (ALI) in mice besides antibacterial activity [31].…”

“…At three days after treatment, TNF-α, IL-6, and MCP-1 in the serum of the amphenmulin treatment group were significantly decreased than those of the infection group (p < 0.05). It has been reported that valnemulin can inhibit TNF-α and IL-6 released by macrophages induced by lipopolysaccharide, indicating that valnemulin has certain anti-inflammatory effect [23]. For both valnemulin and amphenmulin were pleuromutilin derivatives, we are wondering whether amphenmulin could possess anti-inflammatory effect like valnemulin.…”