Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Dexmedetomidine mitigates lipopolysaccharide-induced acute lung injury in septic rats via inhibition of NF-κB associated anti-inflammatory pathway

Hongcheng Zang , Gang Shao

Department of Anesthesiology, The First People’s Hospital of Fuyang District, Hangzhou 311400, PR China;

For correspondence:- Hongcheng Zang Email: j618zn@163.com

Accepted: 15 November 2020 Published: 30 December 2020

Citation: Zang H, Shao G. Dexmedetomidine mitigates lipopolysaccharide-induced acute lung injury in septic rats via inhibition of NF-κB associated anti-inflammatory pathway. Trop J Pharm Res 2020; 19(12):2559-2563 doi: 10.4314/tjpr.v19i12.11

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of dexmedetomidine in a rat model of acute lung injury (ALI), and the underlying mechanism.

Methods: Acute lung injury (ALI) was induced in adult male Sprague Dawley rats (n = 27) using lipopolysaccharide (LPS). Three rat groups were used (9 rats/group): untreated control, LPS and treatment groups. Pathological lesions in rat pulmonary tissues were assessed and inflammatory scores determined. The levels TNF-α and IL-6 in BALF were determined using their respective enzyme-linked immunosorbent assay (ELISA) kits, while protein levels of p-IκB and NF-κB p65 were assessed by Western blotting.

Results: Lung tissue damage was markedly mitigated in treatment mice, relative to LPS mice (p < 0.05). Inflammatory scores and population of neutrophils and macrophages increased significantly in LPS mice, relative to control, but decreased by dexmedetomidine exposure (p < 0.05). Similarly, TNF-α and IL-6 levels in pulmonary tissue homogenates of LPS rats were increased, relative to control rats, but were downregulated by dexmedetomidine exposure (p < 0.05). Moreover, dexmedetomidine downregulated the expressions of p-IκB and NF-κB p65 in pulmonary tissues (p < 0.05).

Conclusion: Dexmedetomidine mitigates LPS-induced ALI in rats by blocking the activation of NF-κB and IκB, coupled with inhibition of the secretion of TNF-α and IL-6.

Keywords: Acute lung injury, Dexmedetomidine, Inflammatory cytokines, NF-κB pathway, Sepsis