Original communicationCytochrome P450 activity mirrors nitric oxide levels in postoperative sepsis: Predictive indicators of lethal outcome
Section snippets
Clinical profile and study design
The study included 42 consecutive patients treated on the surgical intensive care unit (ICU) for clinical sepsis. Sepsis occurred after major visceral surgery in all cases. The Table details the clinical profile of the patients enrolled in the study. Four patients were subjected to neoadjuvant radio- or chemotherapy. Patients on an immunosuppressive regimen and patients with acquired or inherited immune deficiencies were excluded from the study. For the diagnosis of sepsis, patients had to meet
Clinical profile of patients
A total of 42 consecutive patients who developed sepsis (defined by the criteria listed above) after major abdominal surgery were included in the study. The Table sketches the clinical profile of the study population. Overall mortality due to sepsis was 45.2% (19 of 42 patients). Survivors and nonsurvivors did not differ in any of the analyzed clinical parameters, including age, sex, underlying malignant disease, surgical procedures, septic focus, or type of infection (Table).
Increased NO levels during postoperative sepsis
The results of
Role of NO in sepsis and septic shock
During the course of sepsis the synthesis of inducible nitric oxide synthetases (iNOS) is stimulated by endotoxin and cytokines, leading to the production of large amounts of NO over an extended period of time.18, 19 iNOS can be induced in a variety of cells like macrophages, lymphocytes, neutrophils, vascular endothelia, hepatocytes, and Kupfer cells.18, 20, 21, 22 The cytokines mainly involved in the induction of iNOS are TNF-α, IFN-γ, and IL-1. The resulting overproduction of NO causes
Conclusion
NO serum levels as well as aminopyrine breath test (ABT) values in early sepsis could be clinically used for identifying individuals with an increased risk of death due to sepsis. Although the assessment of NO serum levels is time-consuming and expensive, the ABT seems to be an easy-to-perform and inexpensive method for monitoring patients during postoperative sepsis with prognostic as well as therapeutic implications. Low ABT values might aid in the early identification of potential lethal
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High serum nitrates levels in non-survivor COVID-19 patients
2022, Medicina IntensivaCitation Excerpt :Nitric oxide is a very unstable and short half-life gas that breaks rapidly to the stable products as nitrate and nitrite.17,18 Higher blood nitrate and nitrite levels has been found in patients with higher sepsis severity,19–23 and in non-survivor than in survivor septic patients.23 Increased blood nitrate and nitrite levels has been found in COVID-19 patients than in healthy subjects24; however, we have not found data about serum nitrate levels and prognosis of COVID-19 patients.
Blood optical absorption of rats with hepatic damage and turmeric treatment: Methemoglobin analysis
2019, Journal of Molecular LiquidsCitation Excerpt :Blue symbols revealed a new absorption band around 430 nm to 525 nm. One component of this absorption band could be related to the methemoglobin (Mth) [31], another component could be due to the cytochrome P450 (CP450) [32]; this absorption band is not possible to observe from the original absorption spectra (Black symbols). In the group corresponding to liver cancer (Fig. 4B), blue symbols show slightly greater absorption in the range of 450–600 nm, while the group of Sham + Turmeric (Fig. 4C) has a lower absorption compared to the other groups in the same range.
Regulation of Drug-Metabolizing Enzymes and Drug Metabolism by Inflammatory Responses
2017, Drug Metabolism in DiseasesThe effect of inflammation on drug metabolism: A focus on pediatrics
2011, Drug Discovery TodayCitation Excerpt :It is likely that cytokines have an important role in the suppression of CYP activity in these patients. This is further supported by the results of Novotny et al., who found a significant decrease in overall CYP450 activity, measured by the aminopyrine breath test, in patients with sepsis and this reduction was inversely correlated with TNF-α serum levels [26]. In addition, mephenytoin and chlorzoxazone (CYP2C19 and CYP2E1, respectively) metabolism was depressed in severely injured patients, who also display an intense inflammatory response [27].
The Effect of Selective Inhibition of Inducible Nitric Oxide Synthase on Cytochrome P450 After Liver Transplantation in a Rat Model
2008, Transplantation ProceedingsCitation Excerpt :Our data showed that a significant elevation of CYP activity caused by iNOS inhibition reflected graft function.2,3 So far, clinical results after human OLT have revealed that microsomal graft function in acute rejections followed by NO upregulation lead to reduced CYP activity.1,9 As shown in other solid organ transplantation models, acute rejection reactions are frequently associated with elevated NO levels.
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The first two authors contributed equally to this publication.