platonin and Acute-Lung-Injury

Traumatic hemorrhagic shock and subsequent resuscitation may promote bacteria translocation and cause endotoxemia, a two-hit process that will induce severe lung injury. The pathogenesis involves oxidative stress, neutrophil infiltration, and inflammatory response. Platonin, a potent antioxidant, possesses potent anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury in a two-hit model of traumatic hemorrhage/resuscitation and subsequent endotoxemia.. Adult male rats were randomized to receive traumatic hemorrhage/resuscitation plus lipopolysaccharide (HS/L) alone or HS/L plus platonin (200 μg/kg; n = 12 in each group). Sham groups were used simultaneously. At 6 hours after resuscitation, rats were killed and the levels of lung injury were assayed.. Rats treated with HS/L alone had severe lung injury as evidenced by significant alterations in lung function (i.e., arterial blood gas and alveolar-arterial oxygen difference) and histology. Significant increases in polymorphonuclear leukocytes/alveoli ratio (neutrophil infiltration index) and significant increases in the concentrations of inflammatory molecules (including chemokine, cytokine, and prostaglandin E2) and malondialdehyde (lipid peroxidation index) revealed that HS/L caused significant oxidative stress, neutrophil infiltration, and inflammatory response in rat lungs. Moreover, our data revealed that the levels of functional and histologic alteration as well as polymorphonuclear leukocytes/alveoli ratio and the concentrations of inflammatory molecules and malondialdehyde in rats treated with HS/L plus platonin (200 μg/kg) were significantly lower than those treated with HR/L alone.. Platonin mitigates lung injury in a two-hit model of traumatic hemorrhage/resuscitation and endotoxemia in rats.

Topics: Acute Lung Injury; Animals; Disease Models, Animal; Endotoxemia; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Resuscitation; Shock, Hemorrhagic; Thiazoles

Oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by bilateral lower limb ischemia-reperfusion (I/R). Platonin, a potent antioxidant, possesses anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury induced by lower limb I/R.. Forty-eight adult male rats were allocated to receive I/R, I/R plus platonin (100 μg/kg intravenous injection immediately after reperfusion), sham instrumentation, or sham instrumentation plus platonin (denoted as the I/R, I/R-platonin, Sham, or Sham-platonin group, respectively; n = 12 in each group). Bilateral hind limb I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After sacrifice, the degree of lung injury was determined.. Histologic findings revealed moderate inflammation in lung tissues of the I/R group and mild inflammation in those of the I/R-platonin group. Total cell number and protein concentration in bronchoalveolar lavage fluid as well as the leukocyte infiltration and myeloperoxidase activity in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. The pulmonary concentrations of macrophage inflammatory protein-2, interleukin-6, and prostaglandin E(2) of the I/R group were significantly higher than those of the I/R-platonin group. Moreover, the plasma nitric oxide concentration as well as the nitric oxide and malondialdehyde concentrations in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group.. Platonin mitigates acute lung injury induced by bilateral lower limb I/R in rats.

Topics: Acute Lung Injury; Animals; Antioxidants; Chemokine CXCL2; Dinoprostone; Injections, Intravenous; Interleukin-6; Leukocytes; Lower Extremity; Male; Malondialdehyde; Models, Animal; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thiazoles

Enhanced oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by haemorrhagic shock with resuscitation. Platonin, a potent antioxidant, possesses potent anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury in haemorrhagic shock/resuscitation rats.. Seventy-two adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus platonin (10, 50, or 100μg/kg intravenous injection immediately after resuscitation), sham instrumentation (Sham), or Sham plus platonin (100μg/kg) (n=12 in each group). Haemorrhagic shock was induced by blood drawing and mean blood pressure was maintained at 40-45mmHg for 120min. Then, resuscitation was achieved by shed blood/saline mixtures re-infusion. After monitoring for another 8h, rats were sacrificed.. Arterial blood gas and histological findings, in concert with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that haemorrhagic shock/resuscitation caused significant lung injury. Significant increases in concentrations of inflammatory molecules (chemokine, cytokine, and prostaglandin E(2)) as well as nitric oxide and malondialdehyde in lung tissues confirmed that haemorrhagic shock/resuscitation elicited inflammatory response and imposed oxidative stress in rats. Platonin at the dosages of 50 and 100μg/kg, but not 10μg/kg, significantly attenuated the inflammatory response and oxidative stress induced by haemorrhagic shock/resuscitation. Most important, platonin at the dosages of 50 and 100μg/kg, but not 10μg/kg, significantly mitigated the lung injury induced by haemorrhagic shock/resuscitation.. Platonin mitigates acute lung injury in haemorrhagic shock/resuscitation rats.

Topics: Acute Lung Injury; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Intravenous; Male; Rats; Rats, Sprague-Dawley; Resuscitation; Shock, Hemorrhagic; Thiazoles; Treatment Outcome