Diagnostic value of markers of oxidative stress and metabolic disorders in preterm infants in the early neonatal period

Cilj istraživanja bio je procijeniti biljege oksidativnog stresa i metaboličkih poremećaja kod nedonoščadi te ispitati njihovu udruženost s kratkoročnim ishodima u ranom neonatalnom razdoblju kako bi se utvrdili prediktori nepovoljnih ishoda. Istraživanje je obuhvatilo 46 nedonoščadi gestacijske dobi ≤32 tjedna u ranom neonatalnom razdoblju: 1. skupina od 12 nedonoščadi sa smrtnim ishodom i 2. skupina od 34 nedonoščadi s povoljnim ishodom. Biljezi metaboličkih poremećaja, oksidativnog stresa i antioksidantnog sustava analizirani su u pupčanoj krvi i mokraći prvog i drugog dana života. Procjena parametara oksidativnog (8-izoprostan) i antioksi- dantnog sustava (aktivnost katalaze i superoksid dismutaze (SOD)) te metaboličkog stresa (laktat, piruvat, omjer laktata i piruvata (LPR), NAD+/NADH) potvrdila je energetsku neravnotežu i prisutnost tkivne hipoksije kod novorođenčadi s lošim ishodom. Utvrđeni su sljedeći rizični čimbenici nepovoljne prognoze kod novorođenčadi u ranom neonatalnom razdoblju: asfiksija (p=0,038), rana sepsa (p=0,003), intraventrikulsko krvarenje (p=0,029), hiperlaktatemija (p=0,013), povišena razina piruvata (p=0,002), povišen LPR (p=0,008), snižena aktivnost katalaze (p=0,003) i SOD (p=0,001). Logistička regresija pokazala je da je stopa smrtnosti pozitivno pove- zana s asfijksijom, ranom sepsom i razinom laktata te negativno povezana s aktivnošću SOD. U zaključku, intenzivan oksidativni i metabolički stres kod nedonoščadi udružen je s nepovoljnim ishodima u ranom neonatalnom razdoblju. Kombinacija asfiksije i rane sepse zajedno s visokom razinom laktata i sniženom aktivnošću SOD predviđa nepovoljan ishod u ranom neonatalnom razdoblju.The aim of the study was to evaluate the markers of oxidative stress and metabolic disorders in preterm infants and to examine their association with short-term outcomes in the early neonatal period to identify the predictors of unfavourable outcome. The study included 46 preterm infants, gestational age ≤32 weeks, in the early neonatal period, i.e. group 1 of 12 infants with lethal outcome and group 2 of 34 preterm infants with favourable outcome. Markers of metabolic disorders, oxidative stress and antioxidant system were analysed in cord blood and urine on the first/second day of life. Evaluation of oxidative (8-isoprostane) and antioxidant system (catalase and superoxide dismutase (SOD) activity) and metabolic (lactate, pyruvate, lactate to pyruvate ratio (LPR), NAD+/NADH) stress parameters confirmed energy imbalance and presence of tissue hypoxia in preterm newborns with adverse outcomes. The following risk factors of unfavourable prognosis in preterm infants in the early neonatal period were identified: asphyxia (p=0.038), early-onset sepsis (p=0.003), intraventricular haemorrhage (p=0.029), hyperlactatemia (p=0.013), increased pyruvate level (p=0.002), increased LPR (p=0.008), decreased catalase (p=0.003) and SOD (p=0.001) activity. Logistic regression indicated that mortality rate was positively related to asphyxia, early-onset sepsis and lactate level, and negatively related to SOD activity. In conclusion, intensive oxidative and metabolic stress in preterm infants is associated with adverse outcomes in the early neonatal period. A combination of asphyxia and early-onset sepsis together with high lactate level and decreased SOD activity is a predictor of unfavourable out- come in the early neonatal period

Experimental type 2 diabetes mellitus and acetaminophen toxic lesions: glutathione system indices changes

Background. The goal of the research was to study the effect of acetaminophen on major glutathione part of antioxidant system indices in liver homogenate of rats with type 2 diabetes mellitus in time dynamics. Materials and methods. We conducted two series of experiments. In the first series toxic lesion was caused by a single intragastric administration of acetaminophen suspension in 2 % starch solution to animals in a dose of 1250 mg/kg (1/2 LD50). In the second series  the suspension of acetaminophen in 2 % starch solution in a dose of 55 mg/kg was given, which corresponds to the highest therapeutic dose during 7 days. Non-genetic form of experimental type 2 diabetes mellitus was modeled by Islam S., Choi H. method (2007). Activity of glutathione peroxidase (GPx) and glutathione reductase (GR), and contents of reduced glutathione (GSH) were determined in liver homogenate. Results. The obtained results have shown that GR and GPx activity actively decreased after acetaminophen administration in higher therapeutic doses to rats with type 2 DM. However, the changes were less pronounced than in rats with type 2 DM and acute acetaminophen toxic lesions. Conclusion. Results of the research have shown that acetaminophen administration to rats with type 2 DM causes a significant violation of compensatory mechanisms, especially of the enzyme and nonenzyme parts of antioxidant system

Acetaminophen influence on change of endogenous intoxication indices status of plasmatic membranes in rats with type 2 diabetes mellitus

Introduction: Accumulation of excessive amounts of exo- and endotoxins in the body leads to the inevitable occurrence endogenous intoxication. This status is accompanied by a different type of inflammatory processes in the tissues. Middle mass molecules are products of catabolism of endo- and exogenous proteins. Separate fractions of middle molecular peptides have neurotoxic activity, change the membranes permeability, disturb the sodium-potassium balance, transport amino acids, creatinine excretion, protein biosynthesis, tissue respiration, cause microcirculation disorders, and have cytotoxic activity. Transaminases are enzymes that catalyze biochemical reactions progress. Aminotransferases influence on reaction of the formation and decomposition of amino acids and carbohydrates. The aim of the study: The aim of our work was to study endogenous intoxication and status of plasmatic membranes in animals with type 2 diabetes mellitus and acetaminophen toxic lesions. Research materials and methods: We conducted two series of experiments. In the first series toxic lesion was caused by a single intragastric administration of acetaminophen suspension in 2 % starch solution to animals in a dose of 1250 mg/kg (1/2 LD50). In the second series the suspension of acetaminophen in 2 % starch solution in a dose of 55 mg/kg was given. Non-genetic form of experimental type 2 diabetes mellitus was modeled by a single intraperitoneal administration of streptozotocin solution in doses 65 mg/kg, which was diluted by citrate buffer (pH 4.5) with the previous intraperitoneal nicotinamide administration in doses of 230 mg/kg. Rats, which were given the same amount of solvent (citrate buffer pH 4.5), were used as the control group. Results and discussion: Content of middle mass molecules and erythrocyte intoxication index were determined for research of endogenous intoxication status of rats with type 2 diabetes at single administration of acetaminophen. The experimental results show, that all investigated parameters changes compared with intact animals after acetaminophen administration to animals with type 2 diabetes. Aminotransferases are the main enzymes of protein metabolism and combine carbohydrate metabolism. The high levels of these enzymes in the blood are signal of liver tissues damages. The destruction and death of cells in this organ is accompanied by the release of enzymes in the blood.  Conclusion: After analyzing of the obtained results, it can be argued that acetaminophen changes of endogenous intoxication indices and status of plasmatic membranes in rats with type 2 diabetes mellitus