Effects of Isoflurane on Hepatic Injury Associated with HCl/LPS-Induced Acute Lung Injury: A Histopathological and Molecular Study

Background: Acute lung injury (ALI) is a severe inflammatory condition that can trigger secondary damage in distant organs, including the liver. Although isoflurane has been reported to exert anti-inflammatory and organ-protective effects in various experimental models, its impact on hepatic injury associated with hydrochloric acid (HCl)/lipopolysaccharide (LPS)-induced ALI remains poorly understood. Therefore, this study aimed to evaluate the effects of isoflurane on histopathological and molecular alterations in the liver following HCl/LPS-induced ALI in rats. Materials and methods: Thirty-two male Wistar albino rats were randomly assigned to four groups: Control, HCl/LPS, Early Isoflurane and Late Isoflurane. Histopathological alterations were assessed using semi-quantitative scoring, while the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), Beclin-1, Bax, B-cell lymphoma 2 (BCL-2), and hypoxia-inducible factor-1 alpha (HIF-1α) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, correlations between molecular and histopathological parameters were evaluated using Spearman’s rank correlation analysis. Results: HCl/LPS administration resulted in marked hepatic injury characterized by hepatocellular degeneration, necrosis, inflammatory cell infiltration, Kupffer cell activation, sinusoidal congestion and sinusoidal dilatation. These changes were accompanied by significantly increased TNF-α, IL-6, Beclin-1, Bax and HIF-1α expression levels, an elevated Bax/BCL-2 ratio and decreased BCL-2 expression. Isoflurane administration was associated with significant improvements in histopathological findings and gene expression profiles. Furthermore, significant positive correlations were identified between TNF-α and total liver injury score, IL-6 and inflammatory cell infiltration, Bax and hepatocellular necrosis, and HIF-1α and total liver injury score. Conclusion: In conclusion, isoflurane was associated with attenuation of remote hepatic injury following HCl/LPS-induced ALI, accompanied by altered expression of genes related to inflammation, apoptosis, hypoxia, and autophagy. The present study contributes to the limited literature by providing an integrated histopathological and gene expression evaluation of remote hepatic injury in an HCl/LPS-induced ALI model.