platonin and Endotoxemia

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

Platonin, a cyanine photosensitizing dye, is a potent macrophage-activating agent and an immunomodulator. In this study, we compare the inhibitory effects of platonin with those of the three clinical drugs minocycline, clindamycin, and cyclosporin, on hypotension, tachycardia, and nitric oxide (NO) formation in a rat model of circulatory shock induced by Escherichia coli lipopolysaccharide (LPS). We also evaluate the effect of drugs on the 6 h survival rate in LPS-treated rats. Administration of LPS (15 mg/kg) caused a rapid drop in mean arterial blood pressure (MAP). Minocycline (10 mg/kg, i.v.) significantly prevented the fall of MAP at 3 h, and platonin (100 microg/kg, i.v.) markedly prevented the fall of MAP within the 0-3 h period after LPS administration. However, neither clindamycin (10 mg/kg, i.v.) nor cyclosporin (15 mg/kg, i.v.) had any effects in this study. On the other hand, an inducible NO synthase inhibitor, NG-nitro-L-arginine ester (L-NAME), caused a significantly increase in MAP and a moderate bradycardia after LPS administration. In addition, an increase in plasma nitrate formation elicited by endotoxemia was significantly reduced by pretreatment with either minocycline (10 mg/kg) or platonin (100 microg/kg). However, only platonin (100 microg/kg) markedly reduced the mortality and prolonged the mean survival time in LPS-treated rats. Minocycline, clindamycin, and cyclosporin had no effects under the same conditions. Further studies using an electron spin resonance (ESR) method were conducted on the scavenging activity of platonin on the free radicals formed. Platonin (10 microm) greatly reduced the ESR signal intensity of superoxide anion, hydroxyl radical, and methyl radical formation. In conclusion, platonin has beneficial effects on ameliorating endotoxaemia. This protective effect of platonin may be mediated, at least partly, by the reduced drop in MAP and the inhibition of NO and free radical formation in rat models of endotoxemia.

Topics: Animals; Endotoxemia; Lipopolysaccharides; Male; Photosensitizing Agents; Rats; Rats, Inbred WKY; Shock; Thiazoles