A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome

Dare, Anna J; Phillips, Anthony R.J.; Hickey, Anthony J. R.; Mittal, Anubhav; Loveday, Benjamin; Thompson, Nichola M.; Windsor, John A.

doi:10.1016/j.freeradbiomed.2009.08.019

Cited by 123 publications

(110 citation statements)

References 88 publications

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“…Although protective ventilatory strategies have been shown to lessen mortality in ALI patients (4), the way of directly downregulating inflammation itself has not been fully examined. In addition, there is increasing evidence that oxidative stress as well as nitrosative stress prevails at sites of inflammation as adaptive responses of the host, such as antimicrobial strategies or stress-evoked signal transduction (32,33 (Figure 8). …”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress is potentially cytotoxic and has been implicated in the mechanisms of various diseases, including acute disease such as systemic inflammation or ischemia-reperfusion injury (32,33). There are a number of antioxidants with respective spectrum for neutralizing reactive oxygen species.…”

Section: Pharmacological Attenuation Of Cytomix-induced Cytotoxicity mentioning

confidence: 99%

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Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Section: Pharmacological Attenuation Of Cytomix-induced Cytotoxicity mentioning

confidence: 99%

Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549

et al. 2012

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“…1 Innate immune signaling elicits inflammation by promoting cellular damage such as mitochondrial degeneration, the generation of reactive oxygen species, and the production of proinflammatory cytokines as well as type I interferons. 2 Despite its detrimental effect on hepatocytes, LPS alone causes little hepatocyte death, 3 in contrast to the well-established acute liver injury model of LPS-D-galactosamine (GalN) co-administration. This is in part due to the suppression of LPS-induced autophagy by GalN, 4 suggesting that autophagy is essential for the protection against immune damage in hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

Extrusion of mitochondrial contents from lipopolysaccharide-stimulated cells: Involvement of autophagy

et al. 2015

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Abbreviations: 3MA, 3-methyladenine; CPS1, carbamoyl-phosphate synthase 1, mitochondrial; CASP3, caspase 3, apoptosis-related cysteine peptidase; CTSD, cathepsin D; COX4I1, cytochrome c oxidase subunit IV isoform 1; GalN, D-galactosamine; IL1B, interleukin1, b; LPS, lipopolysaccharide; LAMP, lysosomal-associated membrane protein; MT-mKO1, mitochondrially tagged monomeric Kusabira Orange1; mGFP, monomeric green fluorescent protein; mRFP, monomeric red fluorescent protein; MEF, mouse embryonic fibroblast; PMN, polymorphonuclear leukocyte; SQSTM1/p62, sequestosome 1; tfLC3, tandem fluorescent-tagged LC3; TFEB, transcription factor EB; TNF, tumor necrosis factor; VDAC1, voltage-dependent anion channel 1.Sepsis/endotoxemia is elicited by the circulatory distribution of pathogens/endotoxins into whole bodies, and causes profound effects on human health by causing inflammation in multiple organs. Mitochondrial damage is one of the characteristics of the cellular degeneration observed during sepsis/endotoxemia. Elimination of damaged mitochondria through the autophagy-lysosome system has been reported in the liver, indicating that autophagy should play an important role in liver homeostasis during sepsis/endotoxemia. An increased appearance of mitochondrial DNA and proteins in the plasma is another feature of sepsis/endotoxemia, suggesting that damaged mitochondria are not only eliminated within the cells, but also extruded through currently unknown mechanisms. Here we provide evidence for the secretion of mitochondrial proteins and DNA from lipopolysaccharide (LPS)-stimulated rat hepatocytes as well as mouse embryonic fibroblasts (MEFs). The secretion of mitochondrial contents is accompanied by the secretion of proteins that reside in the lumenal space of autolysosomes (LC3-II and CTSD/cathepsin D), but not by a lysosomal membrane protein (LAMP1). The pharmacological inhibition of autophagy by 3MA blocks the secretion of mitochondrial constituents from LPS-stimulated hepatocytes. LPS also stimulates the secretion of mitochondrial as well as autolysosomal lumenal proteins from wild-type (Atg5 C/C ) MEFs, but not from atg5 ¡/¡ MEFs. Furthermore, we show that direct exposure of purified mitochondria activates polymorphonuclear leukocytes (PMNs), as evident by the induction of IL1B/interlekin-1b, a pro-inflammatory cytokine. Taken together, the data suggest the active extrusion of mitochondrial contents, which provoke an inflammatory response of immune cells, through the exocytosis of autolysosomes by cells stimulated with LPS.

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“…In summary, treatment strategies to control mitochondrial dysfunction include improving the use of oxygen, ATP generation, electron flux transport system, oxidative stress, membrane integrity and a decrease in inflammatory and apoptotic signals [43]. All these therapies have a long way to go before being routinely recommended.…”

Section: Treating the Hypoperfusionmentioning

confidence: 99%

Perfusion Measurement of the Septic Patient in the Emergency Department

Devia-Jaramillo¹

2014

Emergency Medicine

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Sepsis is a deadly disease, more complex and frequent every day, that requires management from different specialists. The emergency physician is the first and one of the most important physicians that has to deal with the septic critically ill patients, because an appropriate initial management is key to a favorable outcome.In the emergency department it can be hard to predict which patients will become sicker just with information from the vital signs, and it's even harder to predict which patients will require a more intensive medical treatment. That is the reason why there must be more resources to measure tissue perfusion in an early and simple way in the emergency room, so that the emergency physician can manage to establish which patients requires earlier intervention to improve their perfusion state, despite not showing any clinically evident signs that help in the diagnosis of their current state.The goal of this paper is to propose a diagnostic and therapeutic algorithm for the hypoperfused patient with septic shock in the emergency department.venous oxygen saturation, arterial and venous lactate, microcirculatory study in different anatomical sites and oxygenation indexes.The emergency department, a place of rapid transit, with time constraints, progressive overcrowding and limited physical space, requires efficient indicators of early appearance and simple implementation in the system. That is why this article aims to show a proposal of early detection of hypoperfusion in the septic patient in the emergency room.

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A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome

Cited by 123 publications

References 88 publications

Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549

Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549

Extrusion of mitochondrial contents from lipopolysaccharide-stimulated cells: Involvement of autophagy

Perfusion Measurement of the Septic Patient in the Emergency Department

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