Time course of liver nitric oxide concentration in early septic shock by cecal ligation and puncture in rats

Eyenga, Pierre; Lhuillier, Franck; Morel, J.; Roussel, Damien; Sibille, Brigitte; Letexier, Dominique; Cespuglio, Raymond; Duchamp, Claude; Goudable, J.; Bricca, Giampiero; Viale, J. P.

doi:10.1016/j.niox.2010.06.002

Cited by 10 publications

(9 citation statements)

References 27 publications

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“…In this study, we used a hypotensive CLP model of severe sepsis that is widely used to investigate the physiologic derangement at the early phase of septic disease in spontaneously breathing [7,17,19] or mechanically ventilated animals [13,15,16]. In accordance with previous studies using the same severe model of sepsis [7,13,15,16,17,18,19], we observed an early arterial hypotension within the rst 3 h (Fig. 1A).…”

Section: Discussionsupporting

confidence: 78%

“…Since the founding work of Hussain et al [2] showed that endotoxin infusion leads to respiratory failure and death, several lines of evidence have shown a relationship between diaphragm weakness following proin ammatory activation of nitric oxide synthase (iNOS) and mitochondrial dysfunction [3,36]. Even though IL-1β may induce diaphragm weakness without any oxidative stress [32], our data along with previous ndings [7,8,17,20] suggest that the intra-diaphragmatic upregulation of IL-1β mRNA leads to an increase in oxidative and nitrosative stress, possibly linked to the stimulation of iNOS upregulation and inhibition of mitochondrial respiration and ATP generation. In regards to those studies, we suggested that the early IL-1β mRNA activation would trigger diaphragm dysfunction through its negative effect upon mitochondrial function and ROS generation.…”

Section: Discussionsupporting

confidence: 68%

“…The experiments were carried out in a rat model of sepsis, as previously described [7,13,17]. In both sham-operated (n = 12) and cecal ligation and puncture (CLP) (n = 12) groups, anesthesia was induced by intraperitoneal injection of sodium pentobarbital (56 mg.kg − 1 ) and fentanyl (20 µg.kg − 1 ) and further maintained by continuous infusion of sodium pentobarbital (56 mg.kg − 1 .h − 1 ) and fentanyl (20 µg.kg − 1 .h − 1 ) administered in saline 0.9%.…”

Section: Animal Proceduresmentioning

confidence: 99%

“…The protocol of CLP was performed to induce sepsis as described previously [7,13,17]. After a stabilization period of 30 min, under an aseptic condition, a 3-cm-long abdominal midline incision was made to expose the cecum at the adjoining intestine in 12 rats of the CLP groups.…”

Section: Animal Proceduresmentioning

confidence: 99%

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Mechanical Ventilation Preserves Diaphragm Mitochondrial Function in a Rat Sepsis Model

Eyenga

Roussel

Rey

et al. 2020

Preprint

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Background: To describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome-c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis.Methods: A cecal ligation and puncture (CLP) protocol was performed in 12 rats while 12 controls underwent sham-operation. Half of the rats in each group were paralyzed and mechanically ventilated. We performed blood gas analysis and lactic acid assays 6 hours after surgery. Afterwards, we measured diaphragm strength and mitochondrial oxygen consumption, ATP and ROS generation, and cytochrome-c oxidase activity. We also measured malondialdehyde (MDA) content as an index of lipid peroxidation, and mRNA expression of the pro-inflammatory interleukin-1β (IL-1β) in diaphragms.Results: CLP rats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLP rats showed lower diaphragm force and increased susceptibility to fatigue, along with depressed mitochondrial oxygen consumption and ATP production and cytochrome-c oxidase activity. These rats also showed increased mitochondrial ROS generation and MDA content. Mechanical ventilation markedly restored mitochondrial oxygen consumption and ATP production in CLP rats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome-c oxidase activity.Conclusion: In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 68%

Section: Animal Proceduresmentioning

confidence: 99%

Section: Animal Proceduresmentioning

confidence: 99%

See 2 more Smart Citations

Mechanical Ventilation Preserves Diaphragm Mitochondrial Function in a Rat Sepsis Model

Eyenga

Roussel

Rey

et al. 2020

Preprint

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“…Em nosso modelo experimental, a administração de LPS elevou significativamente a concentração sérica de nitrato (molécula estável gerada a partir do NO) no intervalo de 6h e 12h. Esse aumento circulante detectado no intervalo de 6h está de acordo com outros trabalhos do nosso laboratório (BATALHÃO et al, 2008;SAIA et al, 2013) e está relacionado à atividade da iNOS, uma vez que outros pesquisadores observaram a expressão proteica da iNOS em fígados de ratos Wistar (SAIA et al, 2013) e de camundongos (CONNELLY;MADHANI;HOBBS, 2005) submetidos à endotoxemia 6 horas após administração de LPS, assim como em fígados de ratos Wistar submetidos à CLP 7h após o início do experimento (EYENGA et al, 2010).…”

Section: Discussionunclassified

Efeito da ghrelina sobre o eixo GH/IGF-1 em animais submetidos à endotoxemia

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À minha orientadora Profª. Drª. Evelin Capellari Cárnio por acreditar em mim e sempre torcer pelo meu sucesso. Por todos momentos que passamos, pelas oportunidades únicas que me concedeu, pelos ensinamentos, ao longo de toda pós-graduação, e pela grande amizade que desenvolvemos. Aos professores que aceitaram participar da minha banca de defesa do doutorado. À Profª. Drª. Angelita Maria Stabile por colaborar com meu trabalho ao realizar, me ensinar e discutir os resultados dos experimentos de Western Blott. Por toda nossa amizade e companheirismo. Ao Prof. Dr. Riccardo Lacchini por colaborar com meu trabalho ao realizar, me explicar e discutir meus resultados dos experimentos de PCR-RT. Aos Professores Dr. José-Antunes Rodrigues e Drª. Lucila Leico K. Elias, pelas dosagens de corticosterona realizada em seu laboratório. À Msc. Patrícia Passaglia por me ajudar durante todo o trabalho, discutindo, ensinando, sugerindo, corrigindo, participando ativamente dos experimentos e agregando valor à minha tese. Ao Msc. e especialista de laboratório Marcelo Eduardo Batalhão pela dosagem de nitrato e por todos os anos de companheirismo, ensinamentos e ajuda. Ao meu Prof. de graduação, Dr. Henry Maia Peixoto, por ser um exemplo de profissional que levo comigo até hoje. Aos meus outros colegas de laboratório, André e Aline, por todos os bons momentos que compartilhamos. Aos meus amigos e familiares de longas datas por fazerem parte da minha história.

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Early septic shock induces loss of oxidative phosphorylation yield plasticity in liver mitochondria

et al. 2014

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We aimed to study the change in mitochondrial oxidative phosphorylation efficiency occurring at the early stage of septic shock in an experimental model. Thirty-six male Wistar rats were divided into two groups. In the first group, a cecal ligation and puncture (CLP) was carried out to induce septic shock for 5 h. The second group includes sham-operated rats and constitutes the control group. Blood gas analysis, alanine amino transferase, and lactic acid dosages were assayed 5 h after surgery. Liver mitochondria were isolated for in vitro functional characterization, including mitochondrial respiratory parameters, oxidative phosphorylation efficiency, oxi-radical production, membrane potential, and cytochrome c oxidase activity and content. Liver interleukin 1β (IL-1β) and tumor necrosis α mRNA levels were determined. Septic shock induced a severe hypotension occurring 180 min after CLP in association with a metabolic acidosis, an increase in plasma alanine amino transferase, liver IL-1β gene expression, and mitochondrial reactive oxygen species production. The rates of mitochondrial oxygen consumption and the activity and content of cytochrome c oxidase were significantly decreased while no alterations in the oxidative phosphorylation efficiency and inner membrane integrity were found. These results show that contrary to what was expected, liver mitochondria felt to adjust their oxidative phosphorylation efficiency in response to the decrease in the mitochondrial oxidative activity induced by CLP. This loss of mitochondrial bioenergetics plasticity might be related to mitochondrial oxidative stress and liver cytokines production.

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Time course of liver nitric oxide concentration in early septic shock by cecal ligation and puncture in rats

Cited by 10 publications

References 27 publications

Mechanical Ventilation Preserves Diaphragm Mitochondrial Function in a Rat Sepsis Model

Mechanical Ventilation Preserves Diaphragm Mitochondrial Function in a Rat Sepsis Model

Efeito da ghrelina sobre o eixo GH/IGF-1 em animais submetidos à endotoxemia

Early septic shock induces loss of oxidative phosphorylation yield plasticity in liver mitochondria

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