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Systemic combined melatonin–mitochondria treatment improves acute respiratory distress syndrome in the rat
Author(s) -
Sun Cheuk Kwan,
Lee Fan Yen,
Kao Ying Hsien,
Chiang Hsin Ju,
Sung Pei Hsun,
Tsai Tzu Hsien,
Lin Yu Chun,
Leu Steve,
Wu Ying Chung,
Lu Hung I,
Chen Yung Lung,
Chung Sheng Ying,
Su Hong Lin,
Yip Hon Kan
Publication year - 2015
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12199
Subject(s) - ards , melatonin , mitochondrion , oxidative stress , endocrinology , medicine , apoptosis , bronchoalveolar lavage , lung , biology , pathology , biochemistry
Despite high in‐hospital mortality associated with acute respiratory distress syndrome ( ARDS ), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin–mitochondria treatment ameliorates 100% oxygen‐induced ARDS in rats. Adult male Sprague‐Dawley rats (n = 40) were equally categorized into normal controls, ARDS , ARDS ‐melatonin, ARDS with intravenous liver‐derived mitochondria (1500 μ g per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin–mitochondria. The results showed that 22 hr after ARDS induction, oxygen saturation (saO 2 ) was lowest in the ARDS group and highest in normal controls, significantly lower in ARDS ‐melatonin and ARDS ‐mitochondria than in combined melatonin–mitochondria group, and significantly lower in ARDS ‐mitochondria than in ARDS ‐melatonin group. Conversely, right ventricular systolic blood pressure and lung weight showed an opposite pattern compared with saO 2 among all groups (all P < 0.001). Histological integrity of alveolar sacs showed a pattern identical to saO 2 , whereas lung crowding score exhibited an opposite pattern (all P < 0.001). Albumin level and inflammatory cells ( MPO +, CD 40+, CD 11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO 2 (all P < 0.001). Protein expression of indices of inflammation ( MMP ‐9, TNF ‐ α , NF ‐ κ B), oxidative stress (oxidized protein, NO ‐1, NOX ‐2, NOX ‐4), apoptosis (mitochondrial Bax, cleaved caspase‐3, and PARP ), fibrosis (Smad3, TGF ‐ β ), mitochondrial damage (cytochrome C), and DNA damage ( γ ‐H2 AX +) exhibited an opposite pattern compared to saO 2 in all groups, whereas protein ( HO ‐1, NQO ‐1, GR , GP x) and cellular ( HO ‐1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin–mitochondria group (all P < 0.001). In conclusion, combined melatonin–mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model.