Didox ameliorates sepsis induced acute lung injury via down regulation of IL-33 signaling pathway in mice

Abstract

NASSER GHALY YOUSIF, ALI NAJAH AL-KHAYYAT, ZAINAB ABD OLKADHIM, NAJAH R. HADI, SARA N. ALTIMIMI, AHMAD ALTIMIMI

Background: Sepsis very well define as life-threatening medical condition and may be characterize as dangerous condition described by dysregulated inflammation. The objective of this study is investigating the effects of pre-treatment with didox in attenuation of acute lung injury caused by sepsis through down regulation of IL-33 pathway. Method and materials: A total of 30 Adult male of Swiss Albino mice were used for the study, with weights ranged between 30 g - 35 g. The experimental animal subjected to cecal ligation and puncture (CLP) and pretreated with 200mg /Kg i.p. of didox 1 hour before sepsis induced. The lung tissue for histopathology examination and proinflammatory markers level (IL-1β, IL-33 and MCP-1) beside serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA). ApHOX analyzer (Nova Biomedical, Waltham, USA) used for the determination of blood gases as indication to lung function in mice groups. Results: When compared the data of different mice sets with the sham collection, levels of serum and lung tissues IL-1β and MCP-1 are showed significant (p<0.001) increased within control and vehicle groups. Sepsis induction set also shows significant (p<0.001) increase in serum IL-33 which cause impairment of lung functions expressed as a significant reduction in partial pressure values for oxygen (pO2) and as well as a significant elevation in partial pressure values for carbon dioxide (pCO2). These changes are consistent with histopathologic examination which shows severe pulmonary damage as compared to sham set. All these changes were counteracted by administration of didox. Conclusions: Our results revealed didox have been shown to decrease sepsis-induced acute lung injury through interfering with inflammatory mediators (IL-1β, IL-33 and MCP-1) and down regulation of IL-33 signaling pathway.