Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2017.02.002
Brazilian Journal of Anesthesiology
Scientific Article

Dexmedetomidine preconditioning protects against lipopolysaccharides-induced injury in the human alveolar epithelial cells

Pré-condicionamento com dexmedetomidina protege contra lesões induzidas por lipopolissacarídeos em células epiteliais alveolares humanas

Lei Zhang; Xian-Jin Zhou; Li-Ying Zhan; Xiao-Jing Wu; Wen-Lan Li; Bo Zhao; Qing-Tao Meng; Zhong-Yuan Xia

http://dx.doi.org/10.1016/j.bjane.2017.02.002 Braz J Anesthesiol, vol.67, n6, p.600-606, 2017
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Abstract

Abstract Background and objectives Dexmedetomidine (DEX) has demonstrated the preconditioning effect and shown protective effects against organize injury. In this study, using A549 (human alveolar epithelial cell) cell lines, we investigated whether DEX preconditioning protected against acute lung injury (ALI) in vitro. Methods A549 were randomly divided into four groups (n = 5): control group, DEX group, lipopolysaccharides (LPS) group, and D-LPS (DEX + LPS) group. Phosphate buffer saline (PBS) or DEX were administered. After 2 h preconditioning, the medium was refreshed and the cells were challenged with LPS for 24 h on the LPS and D-LPS group. Then the malondialdehyde (MDA), superoxide dismutase (SOD), Bcl-2, Bax, caspase-3 and the cytochrome c in the A549 were tested. The apoptosis was also evaluated in the cells. Results Compare with LPS group, DEX preconditioning reduced the apoptosis (26.43% ± 1.05% vs. 33.58% ± 1.16%, p < 0.05) in the A549, which is correlated with decreased MDA (12.84 ± 1.05 vs. 19.16 ± 1.89 nmoL.mg-1 protein, p < 0.05) and increased SOD activity (30.28 ± 2.38 vs. 20.86 ± 2.19 U.mg-1 protein, p < 0.05). DEX preconditioning also increased the Bcl-2 level (0.53 ± 0.03 vs. 0.32 ± 0.04, p < 0.05) and decreased the level of Bax (0.49 ± 0.04 vs. 0.65 ± 0.04, p < 0.05), caspase-3 (0.54 ± 0.04 vs. 0.76 ± 0.04, p < 0.05) and cytochrome c. Conclusion DEX preconditioning has a protective effect against ALI in vitro. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation.

Keywords

Dexmedetomidine, Lipopolysaccharides, Preconditioning, Acute lung injury, Alveolar epithelial cell

Resumo

Resumo Justificativa e objetivos Dexmedetomidina (DEX) demonstrou ter efeito pré-condicionante e também efeitos protetores contra lesão organizada. Neste estudo, com células A549 (células epiteliais alveolares humanas), investigamos se o pré-condicionamento com DEX proporcionaria proteção contra lesão pulmonar aguda (LPA) in vitro. Métodos Células A549 foram aleatoriamente distribuídas em quatro grupos (n = 5): controle, DEX, lipopolissacarídeos (LPS) e D-LPS (DEX + LPS). Administramos solução de PBS (tampão fosfato-alcalino) ou DEX. Após 2 h de pré-condicionamento, o meio foi renovado e as células desafiadas com LPS por 24 h nos grupos LPS e D-LPS. Em seguida, malondialdeído (MDA), superóxido dismutase (SOD), Bcl-2, Bax, caspase-3 e em A549 foram testados. Apoptose também foi avaliada nas células. Resultados Em comparação com o grupo LPS, o pré-condicionamento com DEX reduziu a apoptose (26,43% ± 1,05% vs. 33,58% ± 1,16%, p < 0,05) em células A549, o que está correlacionado com a diminuição de MDA (12,84 ± 1,05 vs. 19,16 ± 1,89 nmol.mg-1 de proteína, p < 0,05) e aumento da atividade de SOD (30,28 ± 2,38 vs. 20,86 ± 2,19 U.mg-1 de proteína, p < 0,05). O pré-condicionamento com DEX também aumentou o nível de Bcl-2 (0,53 ± 0,03 vs. 0,32 ± 0,04, p < 0,05) e diminuiu o nível de Bax (0,49 ± 0,04 vs. 0,65 ± 0,04, p < 0,05), caspase-3 (0,54 ± 0,04 vs. 0,76 ± 0,04, p < 0,05) e citocromo c. Conclusão O pré-condicionamento com DEX tem efeito protetor contra LPA in vitro. Os potenciais mecanismos envolvidos são inibição da morte celular e melhoria da antioxidação.

Palavras-chave

Dexmedetomidina, Lipopolissacarídeos, Pré-condicionamento, Lesão pulmonar aguda, Células epiteliais alveolares

References

Yang B, Huang W, Han J. Study of the role of epidermal growth factor on lung fluid transport in rabbits with acute lung injury caused by endotoxin. Exp Ther Med. 2012;4:611-4.

Vincent JL, Sakr Y, Ranieri VM. Epidemiology and outcome of acute respiratory failure in intensive care unit patients. Crit Care Med. 2003;31:S296-9.

Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 2011;6:147-63.

Ware LB, Matthay MA. The acute respiratory distress syndrome. New Engl J Med. 2000;342:1334-49.

Rubenfeld GD, Herridge MS. Epidemiology and outcomes of acute lung injury. Chest. 2007;131:554-62.

Pang YL, Chen BS, Li SP. The preconditioning pulmonary protective effect of volatile isoflurane in acute lung injury is mediated by activation of endogenous iNOS. J Anesth. 2012;26:822-8.

Li QF, Zhu YS, Jiang H. Isoflurane preconditioning ameliorates endotoxin-induced acute lung injury and mortality in rats. Anesth Analg. 2009;109:1591-7.

Fang B, Li XQ, Bi B. Dexmedetomidine attenuates blood-spinal cord barrier disruption induced by spinal cord ischemia reperfusion injury in rats. Cell Physiol Biochem. 2015;36:373-83.

Wang H, Chen H, Wang L. Acute hyperglycemia prevents dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injury. Acta Cir Bras. 2014;29:812-8.

Tan F, Chen Y, Yuan D. Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats. Biomed Rep. 2015;3:365-70.

Bagcik E, Ozkardesler S, Boztas N. Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia-reperfusion injury in rats. Rev Bras Anestesiol. 2014;64:382-90.

Wang L, Huang H, Fan Y. Effects of downregulation of microRNA-181a on H2O2-induced H9c2 cell apoptosis via the mitochondrial apoptotic pathway. Oxid Med Cell Longev. 2014;2014:960362.

Dong S, Qu X, Li W. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol. 2015;8:43.

Zhang XY, Cao JB, Zhang LM. Deferoxamine attenuates lipopolysaccharide-induced neuroinflammation and memory impairment in mice. J Neuroinflamm. 2015;12:20.

Cui K, Kou JQ, Gu JH. Naja naja atra venom ameliorates pulmonary fibrosis by inhibiting inflammatory response and oxidative stress. BMC Complement Altern Med. 2014;14:461.

Lenaz G. Role of mitochondria in oxidative stress and ageing. Biochim Biophys Acta. 1998;1366:53-67.

Xiao J, Rui Q, Guo Y. Prolonged manganese exposure induces severe deficits in lifespan, development and reproduction possibly by altering oxidative stress response in Caenorhabditis elegans. J Environ Sci. 2009;21:842-8.

Benov L, Batinic-Haberle I. A manganese porphyrin suppresses oxidative stress and extends the life span of streptozotocin-diabetic rats. Free Radical Res. 2005;39:81-8.

Shou-Shi W, Ting-Ting S, Ji-Shun N. Preclinical efficacy of dexmedetomidine on spinal cord injury provoked oxidative renal damage. Ren Fail. 2015;37:1190-7.

Li S, Yang Y, Yu C. Dexmedetomidine analgesia effects in patients undergoing dental implant surgery and its impact on postoperative inflammatory and oxidative stress. Oxid Med Cell Longev. 2015;2015:186736.

Lin WC, Chen CW, Huang YW. Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis. Sci Rep. 2015;5:12463.

Kim W, Youn H, Kang C. Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells. Apoptosis. 2015;20:1242-52.

Wang Z, Wu Q, Nie X. Infusion of esmolol attenuates lipopolysaccharide-induced myocardial dysfunction. J Surg Res. 2016;200:283-9.

Zhao J, Li X, Zou M. miR-135a inhibition protects A549 cells from LPS-induced apoptosis by targeting Bcl-2. Biochem Biophys Res Commun. 2014;452:951-7.

Wolter KG, Hsu YT, Smith CL. Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 1997;139:1281-92.

Haunstetter A, Izumo S. Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ Res. 1998;82:1111-29.

Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770-6.

Veena VK, Popavath RN, Kennedy K. In vitro antiproliferative, pro-apoptotic, antimetastatic and anti-inflammatory potential of 2,4-diacteylphloroglucinol (DAPG) by Pseudomonas aeruginosa strain FP10. Apoptosis. 2015;20:1281-95.

Lee US, Ban JO, Yeon ET. Growth inhibitory effect of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate through induction of apoptotic cell death by increasing DR3 expression in human lung cancer cells. Biomol Ther (Seoul). 2012;20:538-43.

van Heerde WL, Robert-Offerman S, Dumont E. Markers of apoptosis in cardiovascular tissues: focus on Annexin V. Cardiovasc Res. 2000;45:549-59.

Chen SL, Zhou W, Hua FZ. In vitro effect of dexmedetomidine on the respiratory burst of neutrophils. Genet Mol Res. 2016:15.

Whittington RA, Virag L, Gratuze M. Dexmedetomidine increases tau phosphorylation under normothermic conditions in vivo and in vitro. Neurobiol Aging. 2015;36:2414-28.

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