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Tetrahydropyrimidines, ZL-5015 Alleviated Lipopolysaccharide (LPS)-Induced Acute Pneumonia in Rats by Activating the NRF-2/HO-1 Pathway

Wei Sun, Zhou Cheng, Hanyan Chen, Guifen Lin, Hongxing Chen

Department of Emergency, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China (mainland)

Med Sci Monit 2020; 26:e924482

DOI: 10.12659/MSM.924482

Available online: 2020-06-24

Published: 2020-08-26

BACKGROUND: Acute pneumonia is a severe inflammatory disease of the respiratory system. Drugs used to treat acute pneumonia often have strong side effects. Recent studies have shown that tetrahydropyrimidines, ZL-5015 has anti-inflammatory and antitumor effects. However, whether ZL-5015 can relieve symptoms of acute pneumonia is unclear.
MATERIAL AND METHODS: In this study, we used lipo-polysaccharide (LPS) to stimulate SD rats to simulate conditions of acute pneumonia. Diverse doses of ZL-5015 were used for treatment of these rats. After the rates were sacrificed, serum, lung tissue, and bronchoalveolar lavage fluid were collected for the next study. Hematoxylin-eosin (H&E) staining then was used to detect pathologic changes in lung tissues. Enzyme-linked immunosorbent assay was performed to assess levels of inflammatory factors in serum. Commercial kits were used to assess levels of reactive oxygen species (ROS) in bronchoalveolar lavage fluid.
RESULTS: Treatment of ZL-5015 relieved stenosis of the alveolar space and pulmonary edema. Furthermore, levels of inflammatory factors (TNF-alpha, IL-1ß and IL-18) in the lung tissues and serum were downregulated after treatment with ZL-5015. Production of ROS also was suppressed after application of ZL-5015. Moreover, inhibition of expression of NRF-2 and HO-1 was relieved after treatment with ZL-5015. The therapeutic effect of ZL-5015 showed a dose-response relationship.
CONCLUSIONS: ZL-5015 alleviated LPS-induced inflammatory injury and oxidative damage by activating the NRF-2/HO-1 pathway.

Keywords: Abnormalities, Drug-Induced, acute lung injury, Guillain-Barre Syndrome