BACKGROUND: Erythropoietin (EPO) elicits protective effects in lung ischemia-reperfusion, hyperoxia, acute necrotizing pancreatitis, and some other tissues. In the present study, we investigated the possible protective roles of EPO in the lipopolysaccharide (LPS) induced lung injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were treated with EPO (3000 U/kg, i.p.) or vehicle (saline), 30 min prior to LPS administration (6 mg/kg, i.v.). Four h following LPS injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Validated methods were used to measure wet/dry ratios (W/D), myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentrations, and nitrite/nitrate (NO(2)(-)/NO(3)(-)) levels in lungs. Western blotting was performed to study the pulmonary expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine protein. RESULTS: Pretreatment with EPO led to (1) significant attenuation of endotoxemia induced evident lung histologic injury and edema; (2) inhibition of LPS mediated induction in MPO activity and MDA concentration; (3) inhibition of LPS mediated overproduction of pulmonary NO(2)(-)/NO(3)(-) levels; and (4) marked suppression in endotoxin induced expression of iNOS and nitrotyrosine. CONCLUSIONS: This study provides considerable evidence that EPO has an ability to significantly attenuate endotoxin-induced acute lung injury in rats.
BACKGROUND:Erythropoietin (EPO) elicits protective effects in lung ischemia-reperfusion, hyperoxia, acute necrotizing pancreatitis, and some other tissues. In the present study, we investigated the possible protective roles of EPO in the lipopolysaccharide (LPS) induced lung injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were treated with EPO (3000 U/kg, i.p.) or vehicle (saline), 30 min prior to LPS administration (6 mg/kg, i.v.). Four h following LPS injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Validated methods were used to measure wet/dry ratios (W/D), myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentrations, and nitrite/nitrate (NO(2)(-)/NO(3)(-)) levels in lungs. Western blotting was performed to study the pulmonary expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine protein. RESULTS: Pretreatment with EPO led to (1) significant attenuation of endotoxemia induced evident lung histologic injury and edema; (2) inhibition of LPS mediated induction in MPO activity and MDA concentration; (3) inhibition of LPS mediated overproduction of pulmonary NO(2)(-)/NO(3)(-) levels; and (4) marked suppression in endotoxin induced expression of iNOS and nitrotyrosine. CONCLUSIONS: This study provides considerable evidence that EPO has an ability to significantly attenuate endotoxin-induced acute lung injury in rats.
Authors: Hannelore Ehrenreich; Karin Weissenborn; Martin Begemann; Markus Busch; Eduard Vieta; Kamilla W Miskowiak Journal: Mol Med Date: 2020-06-16 Impact factor: 6.354