Use of blood urea nitrogen, creatinine, interleukin-6, granulocyte–macrophage colony stimulating factor in combination to predict the severity and outcome of abdominal sepsis in rats

Gao, Min; Zhang, Lingli; Liu, Ying; Yang, Mingshi; Wang, Nian; Wang, Kangkai; Ou, Danmin; Liu, Meidong; Chen, Guangwen; Liu, Ke; Xiao, Xianzhong

doi:10.1007/s00011-012-0481-3

Cited by 18 publications

(11 citation statements)

References 25 publications

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“…3F) compared with WT. Both BUN and LDH negatively correlate with animal survival after sepsis (19), consistent with our synopsis that KI mice are protected compared with WT. Indeed, KI mice subjected to CLP have attenuated hypothermia (Fig.…”

Section: Resultssupporting

confidence: 88%

Protein kinase G oxidation is a major cause of injury during sepsis

Rudyk¹,

Phinikaridou

Prysyazhna³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Sepsis is a common life-threatening clinical syndrome involving complications as a result of severe infection. A cardinal feature of sepsis is inflammation that results in oxidative stress. Sepsis in wildtype mice induced oxidative activation of cGMP-dependent protein kinase 1 alpha (PKG Iα), which increased blood vessel dilation and permeability, and also lowered cardiac output. These responses are typical features of sepsis and their combined effect is a lowering of blood pressure. This hypotension, a hallmark of sepsis, resulted in underperfusion of end organs, resulting in their damage. A central role for PKG Iα oxidative activation in injury is supported by oxidation-resistant Cys42Ser PKG Iα knock-in mice being markedly protected from these clinical indices of injury during sepsis. We conclude that oxidative activation of PKG Iα is a key mediator of hypotension and consequential organ injury during sepsis.redox | cardiovascular function | endotoxin S epsis, a prevalent medical condition caused by severe infection with systemic inflammation, causes substantial morbidity and mortality (1). Prognosis is poor with 85% survival in uncomplicated sepsis, falling to 20% in those with multiorgan failure (2). The cost of acute care is enormous (3), but survivors often suffer long-term cognitive impairment generating a chronic health care burden (4). Sepsis is characterized by systemic inflammation (5), decreased peripheral vascular resistance (1), microvascular leak (6), and decreased cardiac output (1). The combined effect of these alterations is low blood pressure (hypotension), a major clinical feature of sepsis (1). This hypotension results in underperfusion of end organs that leads to their functional failure and too often patient death (1).Oxidative stress is a hallmark of sepsis, consistent with the inflammatory respiratory burst by neutrophils generating high levels of oxidants (5). However, multiple oxidant-generating systems, including nicotinamide adenine dinucleotide phosphate oxidase, uncoupled nitric oxide synthase (NOS) (7), lysozyme-c (8), and mitochondria (9) are activated during sepsis. Consistent with this, the levels of superoxide and hydroxyl radicals, hydrogen peroxide, peroxynitrite, nitrogen dioxide (7), nitroxyl (10), and nitrosothiols (11) can increase during sepsis. Because oxidants can activate cGMP-dependent protein kinase 1 alpha (PKG Iα) to lower blood pressure (12-14), we hypothesized this process underlies sepsis-induced hypotension and consequential organ injury. Because PKG couples to enhance endothelial permeability (6, 15), oxidative activation would also account for the enhanced microvascular leak that would further exacerbate the hypotension. PKG is also negatively inotropic (13, 16); therefore, oxidative activation might also explain the attenuated cardiac output characteristic of sepsis, further exacerbating the hypotension. Results and DiscussionTo investigate the hypothesis that PKG Iα oxidation mediates septic injury, we used a "redox-dead" Cys42Ser PKG Iα knock-in (KI) mo...

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Section: Resultssupporting

confidence: 88%

Protein kinase G oxidation is a major cause of injury during sepsis

Rudyk¹,

Phinikaridou

Prysyazhna³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Before operation, the rats were fasted for 10–12 hours. According to the process we previously reported [40], rats were weighed and anesthetized by 10% chloral hydrate through intraperitoneal injection, then they underwent laparotomy and ligation of the cecum just below the ileocecal valve with double punctures(18-gauge needle) at the antimesenterial wall for three times. Thereafter, the abdominal wall was closed in two layers.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

Wang

Liu

et al. 2017

Oncotarget

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Resveratrol, a polyphenol compound derived from various edible plants, protects against sepsis-induced acute kidney injury (AKI) via its anti-inflammatory activity, but the underlying mechanisms remain largely unknown. In this study, a rat model of sepsis was established by cecal ligation and puncture (CLP), 30 mg/kg resveratrol was intraperitoneally administrated immediately after the CLP operation. HK-2 cells treated by 1 μg/ml lipopolysaccharide, 0.2 μM tunicamycin, 2.5 mM irestatin 9389 and 20 μM resveratrol were used for in vitro study. The results demonstrated that resveratrol significantly improved the renal function and tubular epithelial cell injury and enhanced the survival rate of CLP-induced rat model of sepsis, which was accompanied by a substantial decrease of the serum content and renal mRNA expressions of TNF-α, IL-1β and IL-6. In addition, resveratrol obviously relieved the endoplasmic reticulum stress, inhibited the phosphorylation of inositol-requiring enzyme 1(IRE1) and nuclear factor-κB (NF-κB) in the kidney. In vitro studies showed that resveratrol enhanced the cell viability, reduced the phosphorylation of NF-κB and production of inflammatory factors in lipopolysaccharide and tunicamycin-induced HK-2 cells through inhibiting IRE1 activation. Taken together, administration of resveratrol as soon as possible after the onset of sepsis could protect against septic AKI mainly through inhibiting IRE1-NF-κB pathway-triggered inflammatory response in the kidney. Resveratrol might be a readily translatable option to improve the prognosis of sepsis.

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“…The outcome of released mediators may be dual -they can be inactivated, but they can also preserve its activity towards endothelial cells, thus creating conditions for hypotension and septic shock (marshall, 2001; Webb, 2002). Gao et al (2012) have noted a significant increase of aST, alT, lDH, CK and creatinine serum level 12 hours from the Clp procedure in rats. These substances regulate the proinflammatory protective immune response to infection and host defense activation of neutrophils, macrophages and lymphocytes, amplify gene expression and release of acute phase proteins and granulocyte colony stimulating factor (GCSF), induce anti-inflammatory cytokines IL-4, IL-6, IL-10, IL-1ra and lower the level of TNf and Il receptors by transformation of growth factor b (opal and 24 hours after the Clp procedure, recorded a significant increase in ALT, AST, LDH, but also a comparable increment in creatinine, lactate, IL-1β, IL-2, IL-6, IL-10, interferon gamma (INF-γ), and TNF-α in the rats' serum.…”

Section: Resultsmentioning

confidence: 93%

Examination of enzymes concentration in the blood of rats with sepsis caused by mixed and pure bacterial cultures

Dragica¹,

Kovačević²,

Zekic³

et al. 2013

ACTA VET-BEOGRAD

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A clinical form of sepsis induced by cecal ligation and puncture (CLP) was caused in order to monitor the concentration of enzymes (alanine aminotransferase -ALT, aspartate aminotransferase -AST, lactate dehydrogenase -LDH, amylase and creatine kinase -CK) in the rat blood. Experiments were performed on male Wistar rats, weighing on average 215±25 g. The rats were divided into four groups. In the first three groups (n=28 per group), sepsis was induced by pure culture of Escherichia coli (EC) or Staphylococcus aureus (SA) and mixed culture (MK) of caecum, while the fourth group included 20 control rats who underwent an abdominal incision. Blood was taken in time intervals of 12, 24, 72 and 120 hours.During the experimental protocol, we identified significant changes of all monitored enzymes in the serum of infected rats. After a period of 12 hours there was a significant increase in ALT (all rats with sepsis), AST and LDH (rats in the MK group) levels, while a decrease was noted in the concentration of amylase (EC, SA). Similarly, 24 hours after the CLP procedure, a significant decrease of amylase (MK) and AST (SA) was recorded, while serum LDH level varied significantly from elevated (EC, SA) to reduced (MC) values. Finally, at the time intervals of 72 and 120 hours the concentration of nearly all monitored enzymes has shown a decline, while significance was noted in lowering of ALT (MK), AST (SA, EC) and amylase (SA) levels. Statistical significance could not be observed in the change of CK levels at any of examined time points.

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Use of blood urea nitrogen, creatinine, interleukin-6, granulocyte–macrophage colony stimulating factor in combination to predict the severity and outcome of abdominal sepsis in rats

Abstract: A combination of different biomarkers improves the diagnostic accuracy and is more effective in the prognosis of sepsis in rats. Use of BUN, Cr, IL-6, GM-CSF in combination to predict the severity and outcome in rats with abdominal sepsis exhibited acceptable diagnostic characteristics.

Cited by 18 publications

References 25 publications

Protein kinase G oxidation is a major cause of injury during sepsis

Protein kinase G oxidation is a major cause of injury during sepsis

Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

Examination of enzymes concentration in the blood of rats with sepsis caused by mixed and pure bacterial cultures

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