Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice

Abstract

This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydrate at 0, 1, 2, 4, 8, 12, 24 and 48 h after treatment administration. Blood samples were collected through cardiac puncture. Lung tissues were stained with haematoxylin and eosin for the observation of lung histology. The degree of pulmonary oedema was determined on the basis of lung wet-to-dry ratio (W/D). The serum activity of cathepsin G was determined through substrate fluorescence assay. The serum levels of endothelial cell-specific molecule-1 (endocan), tumour necrosis factor-a (TNF-a), interleukin-1β (IL-1β), IL-6 and high-mobility group box protein 1 (HMGB1) were determined through enzyme-linked immunosorbent assay. The expression levels of endocan and nuclear NF-κBp65 in the lung were quantified through Western blot. Chymostatin alleviated the pathological changes associated with acute alveolitis in mice; decreased the lung W/D ratio, the activity of cathepsin G and the serum concentrations of TNF-a, IL-1β, IL-6 and HMGB1; and increased the serum concentration of endocan. Western blot results revealed that chymostatin up-regulated endocan expression and down-regulated nuclear NF-κBp65 expression in the lung. Chymostatin reversed the inflammatory effects of paraquat-induced lung injury by inhibiting cathepsin G activity to up-regulate endocan expression and indirectly inhibit NF-κBp65 activity.

Polysaccharide from Spirulina platensis improves sepsis-induced acute lung injury by alleviating inflammatory response and down-regulating endocan expression in rats

“…Our study not only testified that endocan involved in sepsis, but also participated in sepsiscaused acute pulmonary damage. Former study has proved that up-regulation of endocan level can lighten paraquat-triggered lung damage in mice (Yang et al, 2018), and endocan has antiinflammatory property by decreasing the proinflammatory factors levels of TNF-α, IFN-γ, IL-1β, and IL-6, and can relieve acute lung damage caused by LPS (pulmonary epithelium cell apoptosis) (Zhang et al, 2018). In this work, based on the PSP treatment effectively inhibited the inflammatory response and alleviated acute pulmonary damage induced by sepsis, so, the endocan protein level in serum was downregulated in sepsis rats after treating by PSP.…”

Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway

“…Chymase may be involved in the formation of angiotensin II (ANG II), independent of the angiotensin-converting enzymes (ACEs) under inflammatory conditions, cytokines, including tissue growth factor beta (TGF-β), antibacterial peptides, matrix metalloproteinases activation, and extracellular matrix degradation . Conversion of ANG I by chymase may account for 80–90% in the heart and human arteries, and chymostatin was reported to diminish blood pressure in hypertensive rats. , Enhanced chymase activity further contributes to diabetic nephropathy, − angiogenesis, alarmins degradation, lung injury, periodontitis, inflammation during wound healing, and the recruitment of white blood cells in wounded skin . These pathogenic changes, caused by chymase, can be reversed by chymostatin.…”

“…53 Conversion of ANG I by chymase may account for 80−90% in the heart and human arteries, and chymostatin was reported to diminish blood pressure in hypertensive rats. 52,54 Enhanced chymase activity further contributes to diabetic nephropathy, 55−57 angiogenesis, 51 alarmins degradation, 58 lung injury, 59 periodontitis, 60 inflammation during wound healing, 53 and the recruitment of white blood cells in wounded skin. 61 These pathogenic changes, caused by chymase, can be reversed by chymostatin.…”

Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies

“…The fatality rate of PQ poisoning is as high as 50–70% [ 2 ]. PQ absorbed through the digestive tract, skin and respiratory tract can cause multiple organ damage, in which the lung is the primary target organ [ 3 – 5 ]. It is thought that the structural similarity of PQ to lung diamines and polyamines such as putrescine, spermine, and spermidine induces the lung to accumulate PQ competitively [ 6 ].…”