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Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively ( n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45 mmHg for 60 min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression. [ABSTRACT FROM AUTHOR]

Background Oxidation and inflammation caused by lower limb ischemia–reperfusion (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent antioxidative and anti-inflammatory drug, can mitigate lung injury induced by lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated. Materials and methods Adult male Sprague–Dawley rats were randomized to receive I/R, I/R plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 24 h. Results Rats receiving I/R had significant increases in concentrations of nitric oxide, malondialdehyde (lipid peroxidation marker), and inflammatory molecules (including interleukin 6, macrophage inflammatory protein 2, and prostaglandin E 2 ) in plasma, and the lungs, indicating that I/R caused significant oxidation and inflammation in rats. Rats receiving I/R also had significant increases in concentration of phosphorylated inhibitor-κB, indicating that I/R caused significant nuclear factor κB activation. Assays of arterial blood gas, biochemistry, and histopathology confirmed that I/R-induced significant lung injury in rats. Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor κB activation, and lung injury induced by I/R. Of note, cepharanthine significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these previously mentioned effects of cepharanthine were partially reversed by inhibiting the activity of HO-1. Conclusions Cepharanthine mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve its effects on reducing oxidation and inflammation. The mechanisms may also involve enhancing HO-1 expression. [ABSTRACT FROM AUTHOR]

Background: Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO4) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO4 could mitigate I/R-induced lung injury. As MgSO4 is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated. Materials and Methods: Adult male rats were allocated to receive I/R, I/R plus MgSO4 (10, 50, or 100 mg/kg), or I/R plus MgSO4 (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 μg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined. Results: Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E2 concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO4, at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO4. Conclusions: MgSO4 mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels. [Copyright &y& Elsevier]

Background Vascular hyporeactivity contributes to hemodynamic alterations and circulatory failure in severe sepsis. Among the identified mechanisms, inflammation and oxidative stress are the most crucial ones in mediating the development of vascular hyporeactivity induced by sepsis. Platonin, a photosensitive dye and an antioxidant, possesses potent antiinflammation effects. We elucidated whether platonin could mitigate vascular hyporeactivity of thoracic aorta in septic rats. Material and methods Adult male Sprague–Dawley rats were randomized to receive sham operation (Sham), Sham plus platonin (100 μg/kg), cecal ligation and puncture (CLP), or CLP plus platonin (10, 50, or 100 μg/kg) and designated as the Sham, P, CLP, CLP + P(10), CLP + P(50), and CLP + P(100) group, respectively ( n = 6 in each group). After maintaining for 12 hours, surviving rats were euthanized and thoracic aorta was isolated and vascular reactivity of aortic rings was determined. Results Vascular reactivity induced by vasoconstrictors phenylephrine and angiotensin II of the Sham and the P groups ( n = 6 in both groups) were similar, whereas vascular reactivity of the CLP group ( n = 5) were significantly lower than those of the Sham group (both P < 0.001). Of note, vascular reactivity induced by phenylephrine and angiotensin II of the CLP + P(10) group ( n = 5) and the CLP group were not significantly different. In contrast, vascular reactivity induced by phenylephrine and angiotensin II of the CLP + P(50) and the CLP + P(100) groups ( n = 6 in both groups) were significantly higher than those of the CLP group (phenylephrine: P = 0.024 and 0.017; angiotensin II: P = 0.031 and 0.036). Conclusion Platonin could mitigate vascular hyporeactivity of thoracic aorta in septic rats. [ABSTRACT FROM AUTHOR]