Redox Therapy in Neonatal Sepsis

Bajcetic, Milica; Spasić, Snežana; Spasojević, Ivan

doi:10.1097/shk.0000000000000198

Cited by 24 publications

(23 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a cardiomyocyte model of neonatal sepsis, challenge with Gram-negative lipopolysaccharide (LPS) induced NADPH overexpression, leading to COX-2 overexpression through a MAP-kinase/NF- κ B-dependent mechanism [ 19 ]. Therefore, both direct activity of NADPH oxidase and NADPH-induced COX-2 upregulation can contribute to increase cytoplasmic superoxide [ 6 ]. Superoxide is then dismutated to H 2 O 2 by cytoplasmic CuZn-superoxide dismutase (SOD) [ 6 ].…”

Section: Redox Status In Neonatal Sepsismentioning

confidence: 99%

“…SIRS includes inadequate core temperature stability, tachycardia or bradycardia, tachypnea or unexplained need for mechanical ventilation, and leukocyte count elevated or depressed for postnatal age [ 4 ]. It is at present widely accepted that the infective insult due to the invasion of sterile tissues by pathogens merely represents the initiation of sepsis, while the process leading to the sepsis syndrome is subsequently maintained by a cascade of inflammatory and oxidative mechanisms that, once activated, act independently from the presence of the pathogens themselves [ 6 ].…”

Section: Introductionmentioning

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: Redox Status In Neonatal Sepsismentioning

confidence: 99%

Section: Introductionmentioning

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

“…No consented diagnostic and therapeutic guidelines for newborn sepsis have been established. The current therapeutic strategy advocates an early application of an empiric antibiotic treatment if an infection is just suspected [17]. Some antibiotics are applied in terms of an off-label use due to a lack of intervention studies in newborns, raising concerns about their safety [17].…”

Section: Introductionmentioning

confidence: 99%

“…The current therapeutic strategy advocates an early application of an empiric antibiotic treatment if an infection is just suspected [17]. Some antibiotics are applied in terms of an off-label use due to a lack of intervention studies in newborns, raising concerns about their safety [17]. Despite the supportive and antibiotic treatments, congenital infections may still cause long-term complications such as brain damage and neurological sequelae [18].…”

Section: Introductionmentioning

confidence: 99%

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

et al. 2017

View full text Add to dashboard Cite

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections.

show abstract

“…To date, most of sepsis complications remain refractory, and development of novel effective therapeutic approaches is urgently needed. Although the mechanism of sepsis injury is not completely clear, oxidative stress has been believed to play a pivotal role (Bajcetic et al, 2014;Duran-Bedolla et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Amentoflavone prevents sepsis-associated acute lung injury through Nrf2-GCLc-mediated upregulation of glutathione

Zong

Zhang

2016

Acta Biochim Pol

View full text Add to dashboard Cite

Sepsis is a serious medical problem and is one of the main causes of high mortality in intensive care units. Fifty percent of patients with severe sepsis will develop acute lung injury (ALI). Amentoflavone (AMF) is a polyphenolic compound possessing potent anti-inflammatory activities. The study aimed to explore the protective effects of AMF against ALI in cecal ligation and puncture (CLP)-induced septic rats. The results showed that AMF administration protected against septic ALI, as reflected by marked amelioration of histological injury of lung tissues and decrease of pulmonary edema in CLP-treated rats. AMF ameliorated CLP-induced increase of systemic and lung TNFα and IL-1β and binding activity of p65 NF-κB, indicating the inhibition of inflammation. Moreover, AMF prevented CLP-induced oxidative stress, as evidenced by increase of oxygen consumption rate, decrease of TBARS content, increase of SOD activity and GSH level in lung tissue of CLP-treated rats. CLP resulted in significant decrease of mRNA expression of Nrf2 and GCLc, which was inhibited by AMF. AMF-induced protective effects on ALI, inflammation, and oxidative stress were inhibited by lentivirus shRNA-mediated silence of Nrf2 and buthionine sulphoximine (BSO), an inhibitor of GSH synthesis. AMF increased Nrf2-binding activity in GCLc promoters in lung tissue of CLP-treated rats. The results suggested that AMF protected against ALI in septic rats through upregulation of Nrf2-GCLc signaling, enhancement of GSH antioxidant defense, reduction of oxidative stress and final amelioration of inflammation and histological injury of lung. The data provide new therapeutic options for the treatment of sepsis-associated ALI.

show abstract

Redox Therapy in Neonatal Sepsis

Cited by 24 publications

References 81 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

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

Amentoflavone prevents sepsis-associated acute lung injury through Nrf2-GCLc-mediated upregulation of glutathione

Contact Info

Product

Resources

About