The Effects of Methylene Blue on Lung Injury in Septic Rats

Abstract

Purpose: We aimed to investigate the effects of methylene blue (MB) on NO production, myeloperoxidase (MPO) activity, antioxidant status and lipid peroxidation in lung injury during different stages of sepsis in rats. Material and Methods: Rats were randomly divided into 4 groups (n = 20): group C, sham operated; group CMB, sham operated and receiving MB (25 mg/kg, i.p.); group S, sepsis; group SMB, sepsis and receiving MB (25 mg/kg, i.p.). Sepsis was induced by cecal ligation and puncture (CLP). The MB dose was administered after CLP. Each group was subdivided into two subgroups (n = 10) which were sacrificed at 9 or 18 h after the surgical procedure. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and MPO activity, total nitrite/nitrate and malondialdehyde (MDA) in the lung tissue were measured. Lung injury was graded from 1 (injury to 25% of the field) to 4 (diffuse injury) by the pathologist. Results: In group SMB, while SOD and CAT increased in both early and late sepsis periods, GSH-PX increased significantly only in the early sepsis period when compared with group S. Increase in lung MPO activity after CLP-induced sepsis was prevented by MB administration. MB significantly decreased to nitrite/nitrate and MDA levels both in early and late sepsis periods when compared with group S (p < 0.05). Group S showed a marked increase in neutrophil infiltration into the interstitial space and thickening of the alveolar septa, whereas the alveolar damage score was lower in the SMB group (p < 0.05). Conclusion: MB reduced the MPO activity and lipid peroxidation by both decreasing oxidative stress and NO overproduction in the lungs, which resulted in the attenuation of lung injury after CLP-induced sepsis in rats.

Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection

“…As a century-old drug, MB has been in medical use for many years in various pathological conditions (41,42). The therapeutic potential of MB has been demonstrated clinically against many diseases, including endotoxin-induced lung injury, bacterial lipopolysaccharide-induced fever (43)(44)(45), cyclosporin-induced kidney injury (46), doxorubicin-induced heart injury (47), and pancreas injury induced by streptozotocin (48). Recently, MB was reported to attenuate Tau aggregation, and it is currently in phase II clinical trials for treatment of Alzheimer disease.…”

Methylene Blue Protects Liver Oxidative Capacity after Gut Ischaemia–Reperfusion in the Rat

“…MB might modulate the nitric oxide (NO)/guanylate cyclase pathway and reduce oxidative stress and/or might interact directly with mitochondria. 13,14,31 MB passes through both cellular and mitochondrial membranes, accumulates within mitochondria and improves mitochondrial respiration at low concentrations (0.5e2 mM) by shuttling electrons to oxygen in the electron transport chain. MB also counteracts perturbed mitochondrial metabolism induced by mutagens, acts as an alternative electron acceptor in mitochondria and might inhibit the production of superoxide by competing directly with molecular oxygen.…”

Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis

“…ROS production exceeding the antioxidant capacity causes lipid peroxidation and consequent tissue injury and cell death (9,56). MDA is the end-product of fatty acid peroxidation and is generated within inflammatory cells.…”