Crocin Suppresses Inflammatory Response in LPS-Induced Acute Lung Injury (ALI) Via Regulation of HMGB1/TLR4 Inflammation Pathway

Abstract

Acute lung injury (ALI) is a frequent consequence which has high morbidity and mortality in sepsis. The most significant pathogen hypothesized to be causing the formation of ALI in sepsis is thought to be lipopolysaccharide (LPS), a key endotoxin component of gram-negative bacteria. Although endotoxin-induced inflammation is a complex process, it can be artificially produced via administration of lipopolysaccharide (LPS) in Experimental sepsis models. The main objective of thisstudy isto determine possible anti-inflammatory effects of crocin (CRO) which has many biological properties such as anti-inflammatory, antioxidant, and anti-apoptotic in LPS-induced ALI. For this purpose, total 40 Wistar albino rats randomly divided into four groups, ten rats in per group: Control (no treatment), CRO (given 50 mg/kg crocin for 9 days), LPS (given 30 mg/kg LPS at 9th day), LPS+CRO (given 50 mg/kg crocin for 9 days and 30 mg/kg LPS at 9th day). After experimental protocol, rats were sacrificed and lung tissues were extracted for further analysis. Histological examinations were performed for detecting histopathological changes in the lung tissue and the changes in the HMGB1 and TLR4 expressions were determined via immunohistochemical staining. Hemorrhage, mononuclear cell infiltration and HMGB1 and TLR4 expressions significantly increased in the LPS group (p<0.05). However, CRO administrations exerted a strong protective effect on the lung tissues in terms of these parameters in LPS+CRO group (p<0.05). According to our results, we suggest that CRO can be considered as a protective agent against bacterial endotoxin induced ALI via inhibition of HMGB1/TLR4 pathway-mediated inflammatory response.