Methylene Blue Alleviates Inflammatory and Oxidative Lung Injury in a Rat Model of Feces-Induced Peritonitis

Abstract

Background and Objectives: Feces-induced peritonitis (FIP), a clinically relevant model of polymicrobial sepsis, induces systemic inflammation and acute lung injury (ALI). Methylene blue (MB), a phenothiazine-based compound, exhibits vasoregulatory, antioxidant, and anti-inflammatory properties in the context of sepsis. This study aimed to evaluate the protective effects of MB on pulmonary injury in a rat model of FIP-induced sepsis. Materials and Methods: Forty male Wistar rats were randomly assigned to four groups: control, FIP, FIP + Saline, and FIP + MB. MB was administered intraperitoneally at a dose of 20 mg/kg, 1 h after FIP induction. At 24 h post-induction, plasma levels of inflammatory markers [interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP)], oxidative stress marker [malondialdehyde (MDA)], metabolic indicator [lactic acid], and vascular signaling marker [cyclic guanosine monophosphate (cGMP)] were measured. Lung injury was evaluated through histopathological analysis and thoracic computed tomography (CT)-based Hounsfield unit (HU) quantification, while pulmonary function was assessed via arterial blood gas analysis, including arterial oxygen pressure (PaO2) and carbon dioxide pressure (PaCO2). Results: FIP induction led to significant increases in plasma levels of IL-6, IL-1 beta, TNF-alpha, CRP, MDA, cGMP, and lactic acid, accompanied by elevated CT attenuation (HU) values and a marked reduction in arterial PaO2 and PaCO2. MB treatment significantly decreased the levels of IL-6, IL-1 beta, TNF-alpha, CRP, MDA, lactic acid, and cGMP, improved PaO2, and attenuated both histopathological lung injury and CT-assessed parenchymal density. No significant differences were observed in PaCO2 among the groups. Conclusions: MB mitigates inflammation, oxidative damage, and pulmonary dysfunction in FIP-induced sepsis. Further studies are warranted to optimize dosing and timing and to evaluate long-term outcomes.