Effect of penehyclidine hydrochloride on IL-6, TNF-α, HIF- 1α and oxidative stress in lung tissue of young rats with acute lung injury

Zhenjiao Fang,Jihong Shu,Xinjun Xiong

doi:10.4314/tjpr.v19i7.14

Abstract

Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats.Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-α and HIF-1α were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining.Results: The lung tissue levels of IL-6, TNF-α and HIF-1α were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05).Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-α and HIF-1α in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this Keywords: Penehyclidine hydrochloride, Alveolar septum, Acute lung injury, Inflammatory cells, IL-6, TNF-α, HIF-1α, Oxidative stress

Highlights

Acute lung injury (ALI) is a major manifestation of systemic inflammatory response syndrome in the lungs
Serum IL-6, tumor necrosis factor-α (TNF-α) and hypoxia inducible factor-1α (HIF-1α) were determined with enzyme-linked immunosorbent assay (ELISA) (ELISA kit, Elabscience, Wuhan, China), while the activities of MPO and Superoxide dismutase (SOD), and MDA levels in lung tissue were determined spectrophotometrically (450 nm, Intelligent microplate reader, Yunkelong, Wuhan, China)
IL-6, TNF-α and HIF-1α levels in the lung tissue and serum of the two groups treated with penehyclidine hydrochloride (PHC) were significantly lower than the corresponding value in model rats, and decreased with increase in PHC dose

Summary

INTRODUCTION

Acute lung injury (ALI) is a major manifestation of systemic inflammatory response syndrome in the lungs. It refers to injuries in cells of alveolar epithelium and capillary endothelium caused directly and indirectly by pneumonia, sepsis, drowning, fat embolism, alveolar hemorrhage and toxic gas inhalation [1]. Tissue homogenates (5 %) of the right lung lobes of the rats were prepared in normal saline. Serum IL-6, TNF-α and HIF-1α were determined with ELISA (ELISA kit, Elabscience, Wuhan, China), while the activities of MPO and SOD, and MDA levels in lung tissue were determined spectrophotometrically (450 nm, Intelligent microplate reader, Yunkelong, Wuhan, China). Count data are presented as percentage (%), and inter-group comparison was carried out using χ2 test. Values of p < 0.05 were considered statistically significant

RESULTS

DISCUSSION

CONCLUSION

Conflict of interest