Molecular mechanisms of organ damage in sepsis: an overview

Sygitowicz, Grażyna; Sitkiewicz, Dariusz

doi:10.1016/j.bjid.2020.09.004

Cited by 40 publications

(10 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment with ethanol and SL-CLP alter the oxidative state of the kidney (Do Vale et al, 2017;Sygitowicz and Sitkiewicz, 2020). Corroborating previous findings (Silva et al, 2020;Do Vale et al, 2017, we showed that ethanol and SL-CLP induced an increase of similar magnitude in the levels of O 2 − in the renal cortex.…”

Section: Discussionsupporting

confidence: 89%

“…Sepsis triggers a complex response of cellular activation that leads to the release of a multitude of pro-inflammatory mediators. Overproduction of ROS and pro-inflammatory proteins during sepsis leads to end-organ dysfunction, which is a hallmark of sepsis (Sygitowicz and Sitkiewicz, 2020). Moreover, during sepsis, iNOS promotes an exaggerated synthesis of NO leading to cellular toxicity (Lambden, 2019).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system

Sousa

Vale

Nascimento

et al. 2021

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

We tested the hypothesis that ethanol would aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) sepsis in the cardiorenal system and that inhibition of iNOS would prevent such response. Male C57BL/6 mice were treated with ethanol for 12 weeks. One hour before SL-CLP surgery, mice were treated with N6-(1-Iminoethyl)-lysine (L-NIL, 5 mg/kg, i.p), a selective inhibitor of iNOS. A second dose of L-NIL was administered 24 h after SL-CLP surgery. Mice were killed 48 h post-surgery and blood, the renal cortex and left ventricle (LV) were collected for biochemical analysis. L-NIL attenuated the increase in serum creatinine levels induced by ethanol, but not by SL-CLP. Ethanol, but not SL-CLP increased creatine kinase (CK)-MB activity and L-NIL did not prevent this response. In the renal cortex, L-NIL prevented the redox imbalance induced by ethanol and SL-CLP. Inhibition of iNOS also decreased lipoperoxidation induced by ethanol and SL-CLP in the LV. L-NIL prevented the increase of pro-inflammatory cytokines and reactive oxygen species (ROS) induced by ethanol and/or SL-CLP in the cardiorenal system, suggesting that iNOS modulated some of the molecular mechanisms that underlie the deleterious effects of both conditions in the cardiorenal system.

show abstract

Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system

Sousa

Vale

Nascimento

et al. 2021

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Asymmetric breakdown leads to creation of functionally efficient organelles and of mitochondria, in which all damages are accumulated. These dysfunctional mitochondria are eliminated by autophagy [9].…”

Section: Mitochondrial Dynamicsmentioning

confidence: 99%

Organ Damage in Sepsis: Molecular Mechanisms

Sygitowicz¹,

Sitkiewicz²

2021

Infections and Sepsis Development

Self Cite

View full text Add to dashboard Cite

Sepsis is one of the most common reasons for hospitalisation. This condition is characterised by systemic inflammatory response to infection. International definition of sepsis mainly points out a multi-organ dysfunction caused by a deregulated host response to infection. An uncontrolled inflammatory response, often referred to as “cytokine storm”, leads to an increase in oxidative stress as a result of the inhibition of cellular antioxidant systems. Oxidative stress, as well as pro-inflammatory cytokines, initiate vascular endothelial dysfunction and, in consequence, impair microcirculation. Microcirculation damage leads to adaptive modifications of cell metabolism. Moreover, mitochondrial dysfunction takes place which results in increased apoptosis and impaired autophagy. Non-coding RNA, especially miRNA and lncRNA molecules, may play an important role in the pathomechanism of sepsis. Altered expression of various ncRNAs in sepsis suggest, that these molecules can be used not only as diagnostics and prognostic markers but also as the target points in the pharmacotherapy of sepsis. The understanding of detailed molecular mechanisms leading to organ damage can contribute to the development of specific therapy methods thereby improving the prognosis of patients with sepsis.

show abstract

“…Considerable evidence indicates that oxidative stress and mitochondrial dysfunction are common features in the majority of inflammatory states and diseases, acute or chronic [9][10][11]. It is generally accepted that excessive generation of reactive oxygen/nitrogen species and mitochondrial injury driven by an uncontrolled inflammatory response play a central role in the genesis of multiple-organ failure observed in sepsis (for review, see [12][13][14][15][16]). Mitochondrial damage and imbalanced generation of reactive oxygen species (ROS) have been shown to contribute to local inflammatory pathologies induced by LPS of Gram-negative bacteria [17,18].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Mitochondria-Targeted Antioxidants against Inflammatory Response to Lipopolysaccharide Challenge: A Review

Fock

Парнова

2021

Pharmaceutics

View full text Add to dashboard Cite

Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is the most abundant proinflammatory agent. Considerable evidence indicates that LPS challenge inescapably causes oxidative stress and mitochondrial dysfunction, leading to cell and tissue damage. Increased mitochondrial reactive oxygen species (mtROS) generation triggered by LPS is known to play a key role in the progression of the inflammatory response. mtROS at excessive levels impair electron transport chain functioning, reduce the mitochondrial membrane potential, and initiate lipid peroxidation and oxidative damage of mitochondrial proteins and mtDNA. Over the past 20 years, a large number of mitochondria-targeted antioxidants (mito-AOX) of different structures that can accumulate inside mitochondria and scavenge free radicals have been synthesized. Their protective role based on the prevention of oxidative stress and the restoration of mitochondrial function has been demonstrated in a variety of common diseases and pathological states. This paper reviews the current data on the beneficial application of different mito-AOX in animal endotoxemia models, in either in vivo or in vitro experiments. The results presented in our review demonstrate the promising potential of approaches based on mito-AOX in the development of new treatment strategies against Gram-negative infections and LPS per se.

show abstract

Molecular mechanisms of organ damage in sepsis: an overview

Cited by 40 publications

References 80 publications

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system

Organ Damage in Sepsis: Molecular Mechanisms

Protective Effect of Mitochondria-Targeted Antioxidants against Inflammatory Response to Lipopolysaccharide Challenge: A Review

Contact Info

Product

Resources

About