Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients

Objectives: The aim of our study was to determine if redox imbalance caused by the activities of antioxidant enzymes existed in erythrocytes of type 1 myotonic dystrophy ( DM1) patients. Methods: The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were measured in 30 DM1 patients and 15 healthy controls ( HCs). The obtained values were correlated with the Muscular Impairment Rating Scale ( MIRS) score and creatine kinase ( CK). Results: Superoxide dismutase and catalase activities were lower in DM1 patients compared to HCs. A positive correlation was found between disease duration and MIRS score as well as with glutathione reductase activity. In DM1 patients, there were positive correlations between catalase, glutathione peroxidase, and glutathione reductase activities. After sub-dividing DM1 patients according to CK levels, superoxide dismutase activity was still statistically different from HCs. However, catalase activity was significantly lower only in DM1 patients with increased CK. Discussion: Undesirable alterations in antioxidant enzyme activities during DM1 disease progression may result in conditions favoring oxidative stress and changes in metabolism which together could contribute to muscle wasting

Supplementary data for the article: Uzelac, T. N.; Nikolić-Kokić, A. L.; Spasić, S. D.; Mačvanin, M. T.; Nikolić, M. R.; Mandić, L. M.; Jovanović, V. B. Opposite Clozapine and Ziprasidone Effects on the Reactivity of Plasma Albumin SH-Group Are the Consequence of Their Different Binding Properties Dependent on Protein Fatty Acids Content. Chemico-Biological Interactions 2019, 311. https://doi.org/10.1016/j.cbi.2019.108787

Supplementary material for: [https://www.sciencedirect.com/science/article/pii/S0009279719310257?via%3Dihub]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3333]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3865

Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood

Background: Epilepsy is a chronic brain disease affecting millions of people worldwide, but little is known about the impact of anti-seizure medications on redox homeostasis. Methods: This study aimed to compare the effects of the long-term use of oral anti-seizure medications in monotherapy (lamotrigine, carbamazepine, and valproate) on antioxidant enzymes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, haemoglobin, and methaemoglobin content in erythrocytes, and concentrations of total proteins and thiols, nitrites, lipid peroxides and total glutathione in the plasma of epilepsy patients and drug-naïve patients. Results: The results showed that lamotrigine therapy led to lower superoxide dismutase activity (p < 0.005) and lower concentrations of total thiols (p < 0.01) and lipid peroxides (p < 0.01) compared to controls. On the other hand, therapy with carbamazepine increased nitrite levels (p < 0.01) but reduced superoxide dismutase activity (p < 0.005). In the valproate group, only a decrease in catalase activity was observed (p < 0.005). Canonical discriminant analysis showed that the composition of antioxidant enzymes in erythrocytes was different for both the lamotrigine and carbamazepine groups, while the controls were separated from all others. Conclusions: Monotherapy with anti-seizure medications discretely alters redox homeostasis, followed by distinct relationships between antioxidant components

Influence of Radiation Dose in Computed Tomography on Antioxidant Enzyme Activity in Rabbit Erythrocytes

The objective of this study was to assess the radiation dose in computed tomography examinations of rabbits using different examination protocols and to correlate these values with the activity of antioxidant enzymes in their red blood cells following irradiation. The presented results revealed that a single, routine computed tomography scan exposure led to a different response of the activity of antioxidant enzymes in red blood cells regarding both dose and time. The results indicate that there is a dose threshold that is about 25 mGy. Doses below that level do not produce any significant changes in the level of antioxidant enzymes activity. On the other hand, the level just above that threshold had a significant impact on the antioxidant defence, but in a relatively short time period (2 hours after exposure), compared to the higher dose that requires a longer adaptive period

Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients

Ferrous iron, released from iron deposits in the motor cortex and other brain regions of amyotrophic lateral sclerosis (ALS) patients, participates in the Fenton reaction in cerebrospinal fluid (CSF) alongside H(2)O(2), which is continuously released by neuronal cells. In vivo, the production of notoriously reactive hydroxyl radicals via this reaction could lead to the progression of the disease. Herein, we have examined the effect of ascorbate and uric acid on the production of hydroxyl radicals in CSF from both sporadic ALS patients and control subjects. Electron paramagnetic resonance spectroscopy identified ascorbyl radicals in CSF from ALS patients whereas it was undetectable in control CSF. The addition of H(2)O(2) to the CSF from ALS patients provoked further formation of ascorbyl radicals and the formation of hydroxyl radicals ex vivo. The hydroxyl addition of uric acid to CSF from ALS patients diminished the production of hydroxyl radicals. In conclusion, there are clear differences between the roles of the two examined radical scavengers in the CSF of ALS patients indicating that the use of ascorbate could have unfavourable effects in ALS patients.Ministry of Science of the Republic of Serbia [143034B, 143016B

Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia

The effects of H2O2 are widely studied in cell cultures and other in vitro systems. However, such investigations are performed with the assumption that H2O2 concentration is constant, which may not properly reflect in vivo settings, particularly in redox-turbulent microenvironments such as mitochondria. Here we introduced and tested a novel concept of fluctuating oxidative stress. We treated C6 astroglial cells and primary astrocytes with H2O2, using three regimes of exposure - continuous, as well as fluctuating at low or high rate, and evaluated mitochondrial membrane potential and other parameters of mitochondrial activity - respiration, reducing capacity, and superoxide production, as well as intracellular ATP, intracellular calcium, and NF-kappa B activation. When compared to continuous exposure, fluctuating H2O2 induced a pronounced hyperpolarization in mitochondria, whereas the activity of electron transport chain appears not to be significantly affected. H2O2 provoked a decrease of ATP level and an increase of intracellular calcium concentration, independently of the regime of treatment. However, fluctuating H2O2 induced a specific pattern of large-amplitude fluctuations of calcium concentration. An impact on NF kappa B activation was observed for high rate fluctuations, whereas continuous and low rate fluctuating oxidative stress did not provoke significant effects. Presented results outline the (patho)physiological relevance of redox fluctuations.Ministry of Education and Science of the Republic of Serbia [III41005, OI173014, III41014

Differences in direct pharmacological effects and antioxidative properties of mature breast milk and an infant formula

Early onset and exclusive breastfeeding provides a significant health benefit to infants in comparison to infant formulas. There is groving evidence that presence of some specific protein components in mothers milk are responsible for observed significant health benefit in infants feed with mothers milk. The aim of this paper was to compare mature breast milk and a standard infant formula by examining their effects on smooth muscle contraction and their antioxidative properties. Electron paramagnetic resonance (EPR) spin-trapping spectroscopy was used to compare the antioxidative capacities of breast milk (obtained on the 9th week of lactation) with a commercial infant formula against hydroxyl radical production in the Fenton reaction. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and their vitamin C and sulfhydryl group (–SH) contents were determined in the milks. Pharmacological research was performed on the isolated rat uterus. In contrast to the infant formula, breast milk exerted a relaxing effect on isolated non-vascular smooth muscle. Using EPR and the Fenton reaction as a radical-generating system, we showed that breast milk possesses a three-fold higher antioxidative activity against the hydroxyl radical compared to the infant formula. In both samples, generation of the hydroxyl radical (•OH) led to the production of carbon-centered radicals. The ascorbyl radical was detected in breast milk but not in the infant formula. Human milk has direct pharmacological effects and provides better antioxidant protection than the infant formula due to the presence of specific protein components such as human SOD.Poster: [https://cer.ihtm.bg.ac.rs/handle/123456789/5344

Differences in direct pharmacologic effects and antioxidative properties of mature breast milk and infant formulas

Objective: Early-onset and exclusive breast-feeding provides a significant health benefit to infants compared with infant formulas. The aim of this study was to compare mature breast milk with standard infant formulas by examining their effects on non-vascular smooth muscle contraction and their antioxidative properties. Methods: The pharmacologic effects of breast milk and formulas were examined using a model system of the rat uterine smooth muscle contraction. Electron paramagnetic resonance spin-trapping spectroscopy was used to compare the antioxidative capacities of breast milk (obtained in the ninth week of lactation) with commercial infant formulas against hydroxyl radical production in the Fenton reaction. The activities of superoxide dismutase, glutathione peroxidase, and the sulfhydryl group were determined in the breast milk and infant formulas. Results: In contrast to the infant formulas, breast milk exerted a relaxing effect on isolated non-vascular smooth muscle. In general, breast milk showed higher antioxidative activity compared with the infant formulas. In all samples, the generation of hydroxyl radicals led to the formation of carbon-centered and ascorbyl radicals. Conclusions: Human milk exerts direct pharmacologic relaxation effects and provides better antioxidant protection compared with infant formulas because of the presence of specific enzymatic components, such as human superoxide dismutase. We propose that these effects should be advantageous to an infant's gastrointestinal tract by supporting the normal work of the smooth musculature and maintaining redox homeostasis and may represent one of the mechanisms by which breast-feeding benefits health