Roflumilast prevented tissue damage caused by lipopolysaccharide-induced sepsis via anti-inflammatory action
PLOS ONE, vol.21, no.6 June, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 21 Issue: 6 June
- Publication Date: 2026
- Doi Number: 10.1371/journal.pone.0350653
- Journal Name: PLOS ONE
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, L'Année philologique, Aerospace Database, BIOSIS, Chemical Abstracts Core, EMBASE, Index Islamicus, Linguistic Bibliography, MEDLINE, Psycinfo, zbMATH, Directory of Open Access Journals, Zoological Record, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Materials Science & Engineering Collection (ProQuest), Pharma Collection (ProQuest), Technology Collection (ProQuest)
- Ondokuz Mayıs University Affiliated: Yes
Abstract
Sepsis is a life-threatening condition characterized by a dysregulated immune response leading to multiple organ dysfunction. Despite the use of antibiotics and anti-inflammatory drugs, recovery remains limited. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, is widely used to mimic sepsis-like conditions in animals. This study investigated the anti-inflammatory and protective effects of Roflumilast at two doses (1.5 and 3 mg/kg) in a single-dose LPS-induced sepsis model. Sepsis was induced in rats by intraperitoneal injection of LPS (30 mg/kg), and Roflumilast was administered for 10 days. Liver and kidney injury were evaluated by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels. Pro-inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were measured using ELISA. Histopathological damage and kidney injury molecule-1 (KIM-1) expression were assessed in major organs. LPS significantly increased biochemical and cytokine markers, causing severe tissue damage. While 1.5 mg/kg Roflumilast showed no protective effects, 3 mg/kg markedly reduced inflammatory and injury markers, improved tissue architecture, and decreased KIM-1 expression. These findings suggest that a higher dose of Roflumilast effectively mitigates LPS-induced systemic inflammation and organ injury, supporting its potential as a therapeutic option for sepsis.