Fenofibrate Mitigates Acute Lung Injury in a Rat Model of Feces-Induced Peritonitis

Abstract

This study aimed to investigate the protective effects of fenofibrate against sepsis-induced acute lung injury using a feces-induced peritonitis (FIP) rat model, with particular emphasis on the modulation of HSP70 and Nrf2 as key cellular defense mechanisms. The FIP model was employed to mimic colon-origin abdominal sepsis, frequently encountered in general surgery, including conditions such as colonic perforation and anastomotic leakage. Thirty male Wistar albino rats were randomly assigned to control, FIP, and FIP + fenofibrate groups. Sepsis was induced by intraperitoneal injection of a fecal-saline suspension. Fenofibrate (100 mg/kg) was administered intraperitoneally after the FIP procedure. After 24 h, lung tissues and blood samples were collected. Assessments included histopathology (H&E staining), thoracic CT imaging, arterial blood gas analysis, ELISA-based quantification of plasma cytokines (IL-6, IL-1 beta, TNF-alpha), MDA for oxidative stress, and lung tissue levels of HSP70 and Nrf2. Feces-induced peritonitis caused severe acute lung injury, evidenced by increased histopathological damage (p < 0.001), impaired gas exchange (PaO2 and PaCO2, p < 0.01), elevated inflammatory cytokines (IL-6, IL-1 beta, TNF-alpha; p < 0.001), increased oxidative stress (MDA, p < 0.001), and suppressed lung Nrf2 and HSP70 expression (p < 0.001). Fenofibrate significantly attenuated lung injury, improved gas exchange (p < 0.05), reduced inflammation (p < 0.01-p < 0.001), decreased MDA (p < 0.001), and increased Nrf2 (p < 0.001) and HSP70 (p < 0.01). Fenofibrate attenuates sepsis-induced acute lung injury by reducing inflammation and oxidative stress while preserving HSP-70 and Nrf2-mediated cytoprotective pathways. These findings are clinically relevant to general surgery, as septic lung injury commonly arises from colon-origin abdominal sepsis, including colonic perforation and anastomotic leakage.