Introduction: Dysregulated immune responses are central to progression of sepsis and closely associated with impaired cellular metabolism. However, most existing studies have focused on late-stage sepsis, leaving metabolic alterations during earlier stages of infection poorly characterised. This study aimed to determine whether immune cell metabolic impairment is already present during uncomplicated infection, prior to the development of sepsis, and to evaluate its potential as an early indicator of immune dysfunction and risk of progression.
Materials and methods: Forty patients with sepsis (fulfilling Sepsis-3 criteria) and 27 patients with uncomplicated infection were recruited from the emergency department along with 20 healthy volunteers. Whole blood samples were collected to assess gene expression, cytokine levels, and cellular metabolic functions, including mitochondrial respiration, oxidative stress, and apoptosis in immune cells.
Results: Mitochondrial respiration was significantly impaired in immune cells from both uncomplicated infection and sepsis patients compared with healthy controls (p < 0.05), with more pronounced impairment in established sepsis. Downregulation of BCL2 and BBC3 gene expression was observed in sepsis patients (p < 0.05), but not in uncomplicated infection, potentially contributing to differences in the severity of metabolic impairment. Impaired mitochondrial respiration was significantly associated with increased mitochondrial oxidative stress (p < 0.05), which was elevated in uncomplicated infection and further increased in sepsis. Oxidative stress levels also correlated with tumour necrosis factor-α (r = 0.330) and the expression of CYCS, TP53, SLC25A24, and TSPO (rs = −0.4926, −0.4422, 0.4382, and 0.4835, respectively). Despite these metabolic alterations, no significant differences in immune cell apoptosis were observed between uncomplicated infection and sepsis patients.
Conclusions: Immune cell metabolic dysfunction is present in patients with uncomplicated infection before the clinical onset of sepsis. Early mitochondrial dysfunction and oxidative stress may represent promising targets for further investigation as early biomarkers of immune dysfunction and sepsis risk.
Tag Archives: oxidative stress
The Use of Pistacia Lentiscus Chia Resin versus Omeprazole in Protecting Male Rats Peptic Mucosa against Cold Restraint Stress
Introduction: Peptic mucosal damage induced by acute stress is a serious cause of morbidity and mortality in critically ill patients. The study aimed to investigate the protective, antioxidant and anti-inflammatory effects of pre-treatment with Chios mastic gum (CMG), a traditionally consumed herbal resin naturally deriving from the trunk of Pistacia Lentiscus var. Chia compared to Omeprazole, a standard medication used in the prevention and treatment of gastritis, against the effects of cold restraint stress (CRS) in rat gastric and colonic mucosa.
Methods: Twenty-one male Wistar rats were randomly assigned to three groups: Control (C), Omeprazole (O), and CMG (M), according to the pre-treatment regime, and were subjected to CRS at 4oC for 3 hours. The gastric and colonic mucosal lesions were histologically assessed. ELISA measured blood concentrations of TNF-α, IL-1β, peroxidase, superoxide dismutase (SOD) and total antioxidant capacity (TEAC).
Results: In both groups, O and M, gastric mucosal hyperemia, haemorrhagic infiltration and mucosal oedema, as well as colonic mucosal hyperaemia and haemorrhagic infiltration were significantly reduced compared to the controls (p<0.05). No significant differences were observed between Groups O and M. TNF-α levels were significantly lower in group M compared to Group O (p=0.013). IL-1β levels were significantly depressed in groups M and O compared to control (p≤ 0.001). The activity of both peroxidase and SOD enzymes decreased in group M compared to group O (p= 0.043 and p=0.047 respectively) and the control (p=0.018 and p< 0.001 respectively). Conclusions: The natural Chios mastic gum is a promising nutritional supplement with protective properties to the peptic mucosa against CRS, exerting anti-inflammatory and antioxidant effects.
Oxidative Stress and Antioxidant Therapy in Critically Ill Polytrauma Patients with Severe Head Injury
Traumatic Brain Injury (TBI) is one of the leading causes of death among critically ill patients from the Intensive Care Units (ICU). After primary traumatic injuries, secondary complications occur, which are responsible for the progressive degradation of the clinical status in this type of patients. These include severe inflammation, biochemical and physiological imbalances and disruption of the cellular functionality. The redox cellular potential is determined by the oxidant/antioxidant ratio. Redox potential is disturbed in case of TBI leading to oxidative stress (OS). A series of agression factors that accumulate after primary traumatic injuries lead to secondary lesions represented by brain ischemia and hypoxia, inflammatory and metabolic factors, coagulopathy, microvascular damage, neurotransmitter accumulation, blood-brain barrier disruption, excitotoxic damage, blood-spinal cord barrier damage, and mitochondrial dysfunctions. A cascade of pathophysiological events lead to accelerated production of free radicals (FR) that further sustain the OS. To minimize the OS and restore normal oxidant/antioxidant ratio, a series of antioxidant substances is recommended to be administrated (vitamin C, vitamin E, resveratrol, N-acetylcysteine). In this paper we present the biochemical and pathophysiological mechanism of action of FR in patients with TBI and the antioxidant therapy available.
Statins as Pleiotropic Modifiers of Vascular Oxidative Stress and Inflammation
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the industrialized world and in the future is expected to be the number one killer worldwide. The main cause underlying CVD is atherosclerosis. A key event in atherosclerosis initiation and progression is oxidative stress through the production of reactive oxygen species as well as endothelial dysfunction. Several pro- inflammatory and anti-inflammatory cytokines and proteins are involved in this process, complemented by activation of adhesion molecules that promote leukocyte rolling, tethering and infiltration into the sub-endothelial space. Statins represent the agent of choice since numerous clinical trials have verified that their pharmacological action extends beyond lipid lowering. Statins demonstrate direct anti-oxidant effects by scavenging free radicals and stimulating anti-oxidant enzymes while acting as regulators for cytokine, protein and adhesion molecule expression, all of which are involved in the atherosclerotic process. Statin use is considered one of the most efficient currently used interventions in managing CVD with the likely hood of remaining so in the near future.










