minocycline and Acute-Lung-Injury

Oxidative stress and inflammatory responses play an important role in acute lung injury (ALI). Although minocycline (MINO) has anti-inflammatory effects and is a promising candidate in treating inflammatory diseases, the effect of MINO on ALI during sepsis is still unclear.. In the present study, a mouse model with intestinal perforation was established. C57BL/6 mice received cecal ligation and puncture (CLP) to induce sepsis-associated ALI. MINO was used to treat the mice via intraperitoneal injection at different doses (negative control, 20 mg/kg, 50 mg/kg and 100 mg/kg, respectively) 24 h after CLP. The severity of lung injury was evaluated by pathological examination, and lung wet / dry weight ratio was calculated to evaluate the severity of pulmonary edema. The changes of TNF-α, IL-1β, IL-6, PGE2, MDA, NF-κB, Nrf2, Keap1 and lncRNA MALAT1 levels in lung tissues of the mice were detected with ELISA, chemical colorimetry, Western blot or qRT-PCR.. MINO ameliorated the lung edema and lung injury of the mice induced by CLP in a dose-dependent manner. MINO administration could significantly down-regulate expressions of TNF-α, IL-6, IL-1β, PGE2 and MDA in lung tissues of the mice. Mechanistically, MINO exerted the effects of anti-inflammation and anti-oxidative stress through down-regulating the expression of MALAT1 and regulating Nrf2/Keap1 and NF-κB signaling pathways.. MINO represses oxidative stress and inflammatory response during sepsis-induced ALI via down-regulating MALAT1 expression, and it has the potential to treat septic ALI.

Topics: Acute Lung Injury; Animals; Dinoprostone; Interleukins; Kelch-Like ECH-Associated Protein 1; Lung; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Minocycline; NF-E2-Related Factor 2; Oxidative Stress; RNA, Long Noncoding; Sepsis; Tumor Necrosis Factor-alpha

Since the invention of the heart-lung machine paediatric cardiac surgery developed rapidly. For correction of complex cardiac malformations the application of a cardio-pulmonary bypass (CPB) has become indispensable but possible negative effects of this technique should not be neglected. Especially, both bypassed organs i.e. heart and lung are not perfused during the procedure and therefore are threatened by ischemia and reperfusion injury. Additionally, CPB was developed with a non-pulsatile flow but there are clinical observations that pulsatile flow might be superior with improved patient outcomes. Thus, the aim of our study was to evaluate the effect of CPB on lung structure and to assess whether different flow modalities (pulsatile vs. non-pulsatile flow) or application of the antibiotic minocycline might be advantageous. Thirty five piglets of four weeks age were examined and divided into five experimental groups: control (no CPB) without or with minocycline, CPB (non-pulsatile flow) without or with minocycline and CPB with pulsatile flow. CPB was performed for 90 min followed by a 120 min reperfusion and recovery phase. Thereafter, adenosine triphosphate-content of lung biopsies and histology was carried out. We found that CPB was associated with a significant thickening of alveolar wall accompanied by an infiltration of neutrophil leucocytes. Moreover, markers for hypoxia, apoptosis, nitrosative stress, inflammation and DNA damage were significantly elevated after CPB. These cellular damages could be partially inhibited by minocycline or pulsatile flow. Both, minocycline and pulsatile flow attenuate lung damage after CPB.

Topics: Acute Lung Injury; Adenosine Triphosphate; Animals; Anti-Bacterial Agents; Cardiopulmonary Bypass; Lung; Minocycline; Neutrophil Infiltration; Pulsatile Flow; Swine; Tumor Necrosis Factor-alpha