Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model

Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada A; Kato, Tatsuya; Sugiura, T.; Kakita, Hiroki; Nobata, Masanori; Kamei, Michi; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika

doi:10.1038/pr.2012.134

Cited by 12 publications

(13 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The infusion of endothelin receptor antagonist ETR-P1/fl was proved effective in reducing serum nitrite and nitrate, TNF-alpha, and HMBG-1 in a piglet model of neonatal sepsis and also in reducing pulmonary hypertension and increasing mean arterial pressure and survival time [ 123 ] ( Table 3 ). In accordance with this study, in the same animal model, treatment with ETR-P1/fl reduced TH, OSI (calculated as total hydroperoxide/biological antioxidant potentials), and IL-6 at 3 and 6 hours after CLP, indicating attenuation of prooxidant and proinflammatory insult [ 124 ]. At present, endothelin receptor antagonists have never been investigated in clinical settings in the newborn.…”

Section: Antioxidant Strategies In Neonatal Sepsissupporting

confidence: 66%

“…Most of the studies assessing antioxidant enzyme activity in neonatal sepsis were based on serum measurements that could be influenced by hemolysis processes and in fact provided partially different evidences in comparison to observations based on erythrocyte level measurements [ 68 ]. Moreover, data obtained from animal studies on oxidative stress markers or antioxidant treatments in neonatal sepsis may not strictly reflect the clinical conditions of septic newborns, as in experimental settings, the animal models are challenged with high levels of LPS or bacteria, which is often not the case in clinical practice [ 52 , 53 , 117 , 118 , 123 , 124 ]. As regard to clinical observations, not all of the studies reported rigorous inclusion criteria, defining whether both EOS and LOS or only one of the two categories is included; therefore, conclusions derived from these studies could be misleading as redox pathophysiology of EOS and LOS could be partially different.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sepsis and Oxidative Stress in the Newborn: From Pathogenesis to Novel Therapeutic Targets

Poggi

Dani

2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Sepsis is at present one of the leading causes of morbidity and mortality in the neonatal population. Together with inflammation, oxidative stress is involved in detrimental pathways activated during neonatal sepsis, eventually leading to organ dysfunction and death. The redox cascade during sepsis is mainly initiated by IL-6 and IL-8 stimulation in newborns and includes multiple noxious processes, as direct cell damage induced by reactive oxygen species, activation of gene expression leading to amplification of inflammation and oxidative stress, and impairment of mitochondrial function. Once proinflammatory and prooxidant pathways are established as stimulated by causing pathogens, self-maintaining unfavorable redox cycles ensue, leading to oxidative stress-related cellular damage, independently from the activating pathogens themselves. Despite antioxidant systems are induced during neonatal sepsis, as an adaptive response to an increased oxidative burden, a condition of redox imbalance favoring oxidative pathways occurs, resulting in increased markers of oxidative stress damage. Therefore, antioxidant treatment would exert beneficial effects during neonatal sepsis, potentially interrupting prooxidant pathways and preventing the maintenance of detrimental redox cycles that cannot be directly affected by antibiotic treatment. Among others, antioxidant agents investigated in clinical settings as adjunct treatment for neonatal sepsis include melatonin and pentoxifylline, both showing promising results, while novel antioxidant molecules, as edaravone and endothelin receptor antagonists, are at present under investigation in animal models. Finally, mitochondria-targeted antioxidant treatments could represent an interesting line of research in the treatment of neonatal sepsis.

show abstract

Section: Antioxidant Strategies In Neonatal Sepsissupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Sepsis and Oxidative Stress in the Newborn: From Pathogenesis to Novel Therapeutic Targets

Poggi

Dani

2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Naringenin inhibited O 2 − -induced prepro-ET-1 mRNA expression. Furthermore, activation of the ET receptors promotes oxidative stress and reduces the free radical scavenging ability [ 58 ]. Therefore, it is likely that ET-1 also contributes to the regulation of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Naringenin Inhibits Superoxide Anion-Induced Inflammatory Pain: Role of Oxidative Stress, Cytokines, Nrf-2 and the NO−cGMP−PKG−KATPChannel Signaling Pathway

et al. 2016

View full text Add to dashboard Cite

In the present study, the effect and mechanism of action of the flavonoid naringenin were evaluated in superoxide anion donor (KO2)-induced inflammatory pain in mice. Naringenin reduced KO2-induced overt-pain like behavior, mechanical hyperalgesia, and thermal hyperalgesia. The analgesic effect of naringenin depended on the activation of the NO−cGMP−PKG−ATP-sensitive potassium channel (KATP) signaling pathway. Naringenin also reduced KO2-induced neutrophil recruitment (myeloperoxidase activity), tissue oxidative stress, and cytokine production. Furthermore, naringenin downregulated KO2-induced mRNA expression of gp91phox, cyclooxygenase (COX)-2, and preproendothelin-1. Besides, naringenin upregulated KO2-reduced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) mRNA expression coupled with enhanced heme oxygenase (HO-1) mRNA expression. In conclusion, the present study demonstrates that the use of naringenin represents a potential therapeutic approach reducing superoxide anion-driven inflammatory pain. The antinociceptive, anti-inflammatory and antioxidant effects are mediated via activation of the NO−cGMP−PKG−KATP channel signaling involving the induction of Nrf2/HO-1 pathway.

show abstract

“…Clinical and experimental data indicate that ET-1 is involved in the pathogenesis of sepsis [8, 47, 50], viral and bacterial pneumonia [9, 10], Rickettsia conorii infections [11], Chagas disease [13, 48], and severe malaria [15, 17, 51, 52]. ET-1 is associated with vasospasms, vascular damage, blood brain barrier (BBB) permeability, cardiovascular remodeling, and inflammation [19, 20, 46, 53, 54].…”

Section: Introductionmentioning

confidence: 99%

“…High levels of ET-1 are found in alveolar macrophages, leukocytes [5] and fibroblasts [6]. Clinical and experimental data indicate that ET-1 is involved in the pathogenesis of sepsis [7, 8], viral and bacterial pneumonia [9, 10], Rickettsia conorii infections [11], Chagas disease [12, 13], and severe malaria [14-17]. In this minireview, we will discuss the role of endothelin in the pathogenesis of infectious processes.…”

mentioning

confidence: 99%

Endothelin-1 and its role in the pathogenesis of infectious diseases

et al. 2014

View full text Add to dashboard Cite

Endothelins are potent regulators of vascular tone, which also have mitogenic, apoptotic, and immunomodulatory properties [1-3]. Three isoforms of endothelin have been identified to date, with endothelin-1 (ET-1) being the best studied. ET-1 is classically considered a potent vasoconstrictor. However, in addition to the effects of ET-1 on vascular smooth muscle cells, the peptide is increasingly recognized as a pro-inflammatory cytokine [4, 5]. ET-1 causes platelet aggregation and plays a role in the increased expression of leukocyte adhesion molecules, the synthesis of inflammatory mediators contributing to vascular dysfunction. High levels of ET-1 are found in alveolar macrophages, leukocytes [5] and fibroblasts [6]. Clinical and experimental data indicate that ET-1 is involved in the pathogenesis of sepsis [7, 8], viral and bacterial pneumonia [9, 10], Rickettsia conorii infections [11], Chagas disease [12, 13], and severe malaria [14-17]. In this minireview, we will discuss the role of endothelin in the pathogenesis of infectious processes.

show abstract

Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model

Cited by 12 publications

References 38 publications

Sepsis and Oxidative Stress in the Newborn: From Pathogenesis to Novel Therapeutic Targets

Sepsis and Oxidative Stress in the Newborn: From Pathogenesis to Novel Therapeutic Targets

Naringenin Inhibits Superoxide Anion-Induced Inflammatory Pain: Role of Oxidative Stress, Cytokines, Nrf-2 and the NO−cGMP−PKG−KATPChannel Signaling Pathway

Endothelin-1 and its role in the pathogenesis of infectious diseases

Contact Info

Product

Resources

About