Time Response of Oxidative/Nitrosative Stress and Inflammation in LPS-Induced Endotoxaemia—A Comparative Study of Mice and Rats

Steven, Sebastian; Dib, Mobin; Roohani, Siyer; Kashani, F. Ravandi; Münzel, Thomas; Daiber, Andreas

doi:10.3390/ijms18102176

Cited by 29 publications

(25 citation statements)

References 32 publications

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“…Nevertheless, the venous HbNO content was clearly increased (by~70%) in freshly drawn blood from cav-1 (-/-) mice compared with their wild-type littermate, corroborating the idea that erythrocyte HbNO content mostly reflects NO bioavailability from the vascular wall. This is in line with recent independent observations of increased HbNO in endotoxemic rodents after iNOS induction by lipopolysaccharide injection [ 47 ]. As mature erythrocytes are anucleated and cannot express iNOS upon acute induction [ 7 ], their HbNO content again mainly originates from external (e.g.…”

Section: Discussionsupporting

confidence: 93%

Nitrosyl-hemoglobin formation in rodent and human venous erythrocytes reflects NO formation from the vasculature in vivo

2018

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Reduced bioavailability of nitric oxide (NO) is a major feature of endothelial dysfunction characteristic of cardiovascular and metabolic diseases but the short half-life of NO precludes its easy quantification in circulating blood for early diagnosis. In erythrocytes, NO can react with hemoglobin to form an iron-nitrosyl complex (5-coordinate-α-HbNO) directly quantifiable by Electron Paramagnetic Resonance spectroscopy (EPR) in mouse, rat and human venous blood ex vivo. However, the sources of the nitrosylating species in vivo and optimal conditions of HbNO preservation for diagnostic use in human erythrocytes are unknown. Using EPR spectroscopy, we found that HbNO stability was significantly higher under hypoxia (equivalent to venous pO2; 12.0±0.2% degradation of HbNO at 30 minutes) than at room air (47.7±0.2% degradation) in intact erythrocytes; at 20°C (15.2±0.3% degradation after 30 min versus 29.6±0.1% at 37°C) and under acidic pH (31.7±0.8% versus 62.2±0.4% degradation after 30 min at physiological pH) at 50% of haematocrit. We next examined the relative contribution of NO synthase (NOS) from the vasculature or in erythrocytes themselves as a source of nitrosylating NO. We detected a NOS activity (and eNOS expression) in human red blood cells (RBC), and in RBCs from eNOS(+/+) (but not eNOS(-/-)) mice, as measured by HbNO formation and nitrite/nitrate accumulation. NO formation was increased after inhibition of arginase but abrogated upon NOS inhibition in human RBC and in RBCs from eNOS(+/+) (but not eNOS(-/-)) mice. However, the HbNO signal from freshly drawn venous RBCs was minimally sensitive to the inhibitors ex vivo, while it was enhanced upon caveolin-1 deletion in vivo, suggesting a minor contribution of erythrocyte NOS to HbNO complex formation compared with vascular endothelial NOS or other paracrine NO sources. We conclude that HbNO formation in rodent and human venous erythrocytes is mainly influenced by vascular NO sources despite the erythrocyte NOS activity, so that its measurement by EPR could serve as a surrogate for NO-dependent endothelial function.

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Section: Discussionsupporting

confidence: 93%

Nitrosyl-hemoglobin formation in rodent and human venous erythrocytes reflects NO formation from the vasculature in vivo

2018

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“…Excessive production of inflammation-associated cytokines is a hallmark of endotoxemia [25]. Therefore, we measured four cytokines including pro-inflammatory IL-1β, IL-6, TNF-α, and their counterplayer IL-10 during the whole experiment.…”

Section: Resultsmentioning

confidence: 99%

Kinetics of Physiological and Behavioural Responses in Endotoxemic Pigs with or without Dexamethasone Treatment

Kanitz

Tuchscherer

et al. 2019

IJMS

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Although dexamethasone (DEX) is a widely used immunoregulatory agent, knowledge about its pharmacological properties in farm animals, especially pigs, is insufficient. Previous studies suggest that compared to other species, pigs are less sensitive to the immunosuppression conferred by DEX and more sensitive to the threat of bacterial endotoxins. However, there is a paucity of studies examining DEX immunomodulation in endotoxemia in this species. In this study, a porcine endotoxemia model was established by lipopolysaccharide (LPS) and the effect of DEX-pretreatment on the magnitude and kinetics of neuroendocrine, metabolic, hematologic, inflammatory, and behavioural responses were examined. DEX decreased cortisol, adrenocorticotropic hormone (ACTH), red blood cell, hemoglobin, hematocrit, and lymphocyte whereas glucose concentration was increased under both normal and endotoxemic conditions. By contrast, DEX decreased triglyceride, lactate, and IL-6 concentrations and increased platelet count only under an endotoxemic condition. DEX also reduced the frequency of sickness behaviour following LPS challenge. PCA showed that glucose and triglyceride metabolism together with red blood cell count mainly contributed to the separation of clusters during DEX treatment. Our study demonstrates that DEX protects pigs from inflammation and morbidity in endotoxemia, in spite of their less sensitivity to DEX. Moreover, its considerable role in the regulation of the metabolic and hematologic responses in endotoxemic pigs is revealed for the first time.

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“…Uncontrolled inflammation and excessive oxidative stress may be the leading symptoms of sepsis culminating in multiple organ failure and death (Steven et al 2017). The symptoms of COVID 19 also show an abnormally high inflammatory response (Zhang et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Euglena tuba extract provides protection against lipopolysaccharide-induced inflammatory response and oxidative stress in mice

et al. 2020

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Lipopolysaccharide (LPS), an endotoxin, is known to induce inflammatory response and oxidative stress in rodents. We evaluated the protective role of Euglena tuba extract (ETME) against LPS induced inflammatory response and oxidative stress in male Balb/c mice. Male Balb/c mice were divided into 4 groups. Group 1 (control) were intraperitoneally administered 0.5 mL PBS. Group 2, 3 and 4 were treated with a single dose of LPS (i.p. 40 mg/kg body weight). Prior 1 h, Group 3 and 4 received orally 100 mg/kg body weight and 200 mg/kg body weight ETME respectively. Biomarkers of oxidative stress including TBARS, SOD, Catalase, Liver marker enzyme (SGPT and SGOT), Nitric Oxide, and inflammatory cytokines including IL-6 and TNF-α, were estimated in serum. Oxidative stress and inflammatory markers were significantly increased in the LPS treated group, whereas ETME treated group at different concentrations protected mice from pro inflammatory cytokines and oxidative stress. Our results indicate that 70% methanolic extract of Euglena tuba can efficiently counteract free radical generation and increased level of inflammatory cytokine in an LPS induced mice model.

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Time Response of Oxidative/Nitrosative Stress and Inflammation in LPS-Induced Endotoxaemia—A Comparative Study of Mice and Rats

Cited by 29 publications

References 32 publications

Nitrosyl-hemoglobin formation in rodent and human venous erythrocytes reflects NO formation from the vasculature in vivo

Nitrosyl-hemoglobin formation in rodent and human venous erythrocytes reflects NO formation from the vasculature in vivo

Kinetics of Physiological and Behavioural Responses in Endotoxemic Pigs with or without Dexamethasone Treatment

Euglena tuba extract provides protection against lipopolysaccharide-induced inflammatory response and oxidative stress in mice

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