Tag Archives: oxidative stress

Curcumin exerts protective effects against doxorubicin-induced cardiotoxicity

O. О. Klymenko1*, T. I. Drevytska1, O. O. Gonchar1, K. V. Tarasova2,
V. I. Nosar1, V. Ye. Dosenko1, I. M. Mankovska1

1Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
2Bogomolets National Medical University, Kyiv, Ukraine;
*e-mail: klymenkooks2018@gmail.com

Received: 16 October 2024; Revised: 03 December 2024;
Accepted: 21 February 2025; Available on-line: 03 Marchy 2025

The mechanism of doxorubicin (Dox) cardiotoxicity involves different pathways, including oxidative stress and mitochondrial dysfunction. It’s supposed that pharmacological effect on HIF gene expression may protect the heart against the detrimental effects of the doxorubicin-induced injury. We hypothesized that the cardioprotective effects of Curcumin (Curc) are exerted by regulating HIF and its target genes expression. To test this, an in vitro model of Dox-induced injury to primary myocardial cardiomyocytes was used. Isolated Wistar rat neonatal cardiomyocytes were incubated in the culture medium for 24 h in control, either with Dox (0.5 μmol/ml) or Curc (20 μmol/ml), or in their combination in the same doses. Mitochondria were isolated from rat cardiomyocytes culture. It was demonstrated that cardiomyocytes exposure to Dox led to an increase in the activity of oxidative stress markers in isolated mitochondria, a decrease in the efficiency of the respiratory chain and phosphorylation processes, decline of membrane potential and the rate of K+ ions entry into mitochondria. Doxorubicin inhibited the expression of mRNA of both HIF-1α, 2α, 3α subunits and its important target genes PDK-1 and IGF-1 in mitochondria. A negative impact on the cardiomyocyte contractile activity was observed. The combined use of doxorubicin with curcumin led to an increase of cardiomyocytes viability and attenuation of oxidative stress in mitochondria, prevented the development of mitochondrial dysfunction and significantly improved the contractile activity of cardiomyocytes.

Edaravone reduces the markers of oxidative stress and neuroinflammation in neocortex of rats with acute intracerebral hemorrhage and type 2 diabetes mellitus

V. L. Holubiev*, A. E. Lievykh, V. A. Tkachenko,
Yu. V. Kharchenko, V. I. Zhyliuk

Department of Pharmacology, Dnipro State Medical University, Dnipro, Ukraine;
*e-mail: 209@dmu.edu.ua

Received: 05 August 2024; Revised: 22 October 2024;
Accepted: 21 November 2024; Available on-line: 17 December 2024

Type 2 diabetes mellitus (T2DM) is associated with a higher incidence of hemorrhagic stroke in a severe form. The aim of this study was to estimate the markers of oxidative stress and neuroinflammation in the brain of rats with acute intracerebral hemorrhage (ICH) and T2DM after treatment with edaravone. T2DM was induced by a single intraperitoneal injection of nicotinamide/streptozotocin, ICH – by stereotactic microinjection of bacterial collagenase. Rats were randomized into four groups: 1 – intact control; 2 – T2DM; 3 – T2DM+ICH; 4 – T2DM+ICH+edaravone 6 mg/kg/day. Edaravone (a drug to treat neural injury after acute cerebral ischemic stroke) was administered intraperitoneally for 10 days starting from the 60th day after diabetes mellitus induction and 30 min after ICH induction. Brain homogenates were assessed for the content of advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs). The levels of TNF-α and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured with ELISA. The increased content of 8-OHdG and TNF-α in brain homogenates of animals of T2DM group compared to the control was shown. It was revealed that in brain homogenates of animals of T2DM+ICH group the content of these markers­ significantly exceeds that for T2DM group, and in addition, an elevated AOPPs level was observed. Our results demonstrated that edaravone prevented the elevation of TNF-α level, reduced oxidative DNA damage by decreasing 8-OHdG content, and attenuated the formation of AGEs and AOPPs in the brains of experimental animals. These findings suggest that edaravone may have therapeutic potential in diabetic patients with acute ICH.

Indices of carbohydrate metabolism and antioxidant system state during germination of aged wheat and triticale seeds treated with H(2)S donor

T. O. Yastreb1, A. I. Kokorev1, A. I. Dyachenko2,
M. V. Shevchenko3, M. M. Marenych4, Yu. E. Kolupaev1,4*

1Yuriev Plant Production Institute, National Academy
of Agrarian Sciences of Ukraine, Kharkiv;
2Institute of Cell Biology and Genetic Engineering,
National Academy of Sciences of Ukraine, Kyiv, Ukraine;
3State Biotechnological University, Kharkiv, Ukraine;
4Poltava State Agrarian University, Poltava, Ukraine;
*e-mail: plant_biology@ukr.net

Received: 06 August 2024; Revised: 03 September 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024

Hydrogen sulfide is a gasotransmitter molecule involved in the realization of many functions of the plant organism, including seed germination. Aging of seeds is shown to be accompanied by oxidative stress and reduced germination. The effect of exogenous hydrogen sulfide on the germination of aged cereal seeds has not been studied. The aim of the work was to estimate the effect of priming with NaHS as an H2S donor on wheat and triticale seeds previously subjected to natural aging. Seeds of winter wheat (Triticum aestivum) and winter ×Triticosecale were stored indoors for 4 years at fluctuating temperature and humidity. Aged seeds were treated with 0.2-5 mM NaHS solution for 3 h and germinated in Petri dishes for 3 days. The hydropriming­ treatment was used as a control. Amylase activity in grains, the biomass of shoots and roots, the content of total sugars, H2O2, lipid peroxidation products and anthocyanin, and the activity of antioxidant enzymes in seedlings were determined. It was shown that after the treatment with H2S donor, the activities of catalase and guaiacol peroxidase, as well as the content of anthocyanins were increased only in triticale seedlings. Nevertheless, treatment of seeds of both cereal species was followed by enhanced growth of shoots and roots, increase in amylase and superoxide dismutase activities, decrease in H2O2 and MDA contents, and elevated accumulation of sugars in shoots. It is concluded that the increase in germination of aged cereal seeds under the influence of H2S donor is caused by increased mobilization of reserve carbohydrates and modulation of antioxidant system activity. Such treatment can be considered as an effective tool to improve seedling growth.

Sex differences in respiration and redox homeostasis of heart mitochondria in rats on high-fructose diet

O. Ivanova1, N. Gorbenko1, O. Borikov2, T. Kiprych1, K. Taran1

1SI “V. Danilevsky Institute for Endocrine Pathology Problems
of the NAMS of Ukraine”, Kharkiv, Ukraine;
2V. N. Karazin Kharkiv National University, Kharkiv, Ukraine;
*e-mail: ivolga3006@ukr.net

Received: 05 April 2024; Revised: 27 May 2024;
Accepted: 25 July 2024; Available on-line: 04 September 2024

Sex hormones play a leading role in the sexual dimorphism of mitochondrial dysfunction and oxidative stress that are associated with Metabolic Syndrome (MetS) and considered as possible causes of cardiovascular disease. The aim of the work was to determine mitochondrial respiration and redox homeostasis in the heart mitochondria of high-fructose diet-fed (НFD) rats depending on sex. MetS was induced in Wistar rats by 8 weeks intake of fructose (200 g/l) with drinking water. The experiment was performed on 30 rats divided into five groups: control males, control females, HFD-fed males, HFD- fed females with intact ovaries, ovariectomized HFD-fed females. Heart mitochondria were isolated and indicators of redox homeostasis as well as mitochondrial oxygen consumption rate were determined. Heart mitochondria of intact female rats were characterized by a lower intensity of lipid peroxidation, a higher activity of antioxidant defense system and state 3 respiration in comparison with control males. HFD was shown to induce more expressed oxidative stress due to significant inhibition of enzymatic and non-enzymatic components of antioxidant defese and more pronounced dysregulation of mitochondrial respiration in the heart mitochondria of ovariectomized females as compared to males. This data may partially explain the greater cardiovascular risk in women with low estrogen sufficiency and justify the necessity of new sex-specific prevention and treatment of cardiovascular risk approaches.

Effect of metal nanoparticles usage on oxidative stress indicators and endotoxemia parameters under DMH-induced carcinogenesis

S. B. Kramar1*, I. Ya. Andriichuk2, N. V. Ohinska1, Yu. V. Soroka3,
Z. M. Nebesna1, S. M. Dybkova4, L. S. Rieznichenko4, N. Ye. Lisnychuk2

1Department of Histology and Embryology,
I. Horbachevsky Ternopil National Medical University, Ukraine;
2Central Research Laboratory, I. Horbachevsky Ternopil National Medical University, Ukraine;
3Department of Anaestesiology and Intensive Care,
I. Horbachevsky Ternopil National Medical University, Ukraine;
4F.D. Ovcharenko Institute of Biocolloidal Chemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: kramarsb@tdmu.edu.ua

Received: 10 February 2024; Revised: 19 March 2024;
Accepted: 19 March 2024; Available on-line: 30 April 2024

One of the properties of nanoparticles is their ability to correct manifestations of oxidative stress and endotoxemia, which are critical factors in cancer development. Therefore, the work aimed to investigate the effect of the usage of Au/Ag/Fe nanoparticles on oxidative stress indicators and endotoxemia parameters in experimental colon carcinogenesis. The study was performed on 90 white male rats kept in standard vivarium conditions. The division into groups: I – intact animals; II – intact animals with 21 days NPs administration; III – animals injected with N,N-dimethylhydrazine dihydrochloride for 30 weeks; ІV – animals to which Au/Ag/Fe nanoparticles were intragastrically administered daily for 21 days after induced adenocarcinoma. According­ to our results, the concentration of oxidative stress indicators significantly increases under DMH-induced carcinogenesis conditions. It was established that the 21-day intragastric administration of NP Au/Ag/Fe composition caused a significant (P < 0.001) decrease in the concentration of TBARS in the blood serum by 1.33 times, in the content of diene and triene conjugates by 1.63 and 1.98 times, respectively compared to the third experimental group. The introduction of NPs in the fourth experimental group reduces the concentration of the Schiff bases by 1.34 times (P < 0.001), decreases the content of POMP370 and POMP430 by 1.25 (P < 0.001) and 1.37 times (P < 0.001), respectively, compared to the third experimental group. We also observed the reduction of endotoxemia levels in a fourth experimental animal group based on a significant decrease in MMM indexis and EII percentage.

Antioxidants as supplements during drug-induced thrombocytopenia: a comparative analysis of Vanillic acid, L-carnitine and Caripill™

M. Mithun, V. Rajashekaraiah*

Department of Biotechnology, School of Sciences,
JAIN (Deemed-to-be University), Bengaluru, Karnataka, India;
*e-mail: vani.rs@jainuniversity.ac.in

Received: 20 September 2023; Revised: 07 November 2023;
Accepted: 01 February 2024; Available on-line: 26 February 2024

Drug-induced thrombocytopenia (DIT) is a disorder where platelet count declines as an adverse effect of therapeutic drugs. Plant extract of C. papaya Caripill™ is known to elevate platelet count under thrombocytopenic conditions. To evaluate the contribution of supplements with antioxidant potential to treat DIT, the comparative study of Caripill™, vanillic acid L-carnitine effect on platelet count and indices of oxidative stress in a model of rat thrombocytopenia induced through oral administration of hydroxyurea was performed. Wistar rats were grouped into four categories with five animals in each group: control (without any treatment); control + antioxidants; thrombocytopenia; thrombocytopenia + antioxidants. The above-mentioned antioxidants were supplemented orally at 50 mg/kg for 7 days. The level of lipid peroxidation products­, superoxides, protein carbonyls and sulfhydryls, SOD and CAT activity in isolated platelets as oxidative stress markers, and indices of platelets aggregation and ATP secretion as functional markers were used. Vanillic acid was shown to be beneficial, similar to Caripill™, during hydroxyurea-induced thrombocytopenia by maintaining platelet functions, enhancing both the antioxidant capacity of platelets and its number. L-carnitine efficiently up-regulated the enzymatic antioxidants, maintained platelet functions and protected lipids and proteins from oxidation in thrombocytopenic rats, however, it could not improve the platelet count. These findings open new avenues for employing the studied antioxidants as supplements for therapeutic purposes.

Response of the antioxidant system of wheat seedlings with different genotypes to exogenous prooxidants: the relationship with resistance to abiotic stressors

T. O. Yastreb1,2, A. I. Kokorev2, B. E. Makaova3, N. I. Ryabchun2,
T. V. Sakhno3, A. P. Dmitriev4, Yu. E. Kolupaev2,3*

1Crop Research Institute, Prague, Czech Republic;
2Yuriev Plant Production Institute, National Academy
of Agrarian Sciences of Ukraine, Kharkiv;
3Poltava State Agrarian University, Poltava, Ukraine;
4Institute of Cell Biology and Genetic Engineering, National Academy
of Sciences of Ukraine, Kyiv, Ukraine;
*e-mail: plant_biology@ukr.net

Received: 08 September 2023; Revised: 03 November 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023

Oxidative stress is an important component of heat- and drought-induced damage in plants. However­, information on the relationship between the resistance of cultivated plants with different genotypes to environmental factors and their ability to maintain a pro-/antioxidant balance remains contradictory. This study aimed to compare the growth responses and adaptation ability of the antioxidant system in different wheat cultivars to oxidative stress agents hydrogen peroxide and iron(II) sulfate. Etiolated seedlings of common winter wheat (Triticum aestivum L.) Antonivka and Tobak (heat- and drought-tolerant), and Avgustina and Doskonala (not resistant to heat and drought) were used for the study. Three-day-old etiolated seedlings were exposed to 50 mM H2O2 or 5 mM FeSO4 for one day. It was found that seedlings of Antonivka and Tobak cultivars treated with H2O2 or FeSO4 were able to maintain relatively intensive growth, accumulated significantly lower amounts of endogenous hydrogen peroxide and lipid peroxidation products, significantly increased anthocyanin content and had a higher activity of SOD and catalase as compared with non-resistant cultivars. The non-tolerant cultivars’ response to stress agents was only to increase proline content with a simultaneous decrease in SOD activity and anthocyanins content. The identified varietal markers of the antioxidant system adaptive strategy can be used to develop new approaches for screening wheat cultivars with cross-resistance to major abiotic stressors.

Gamma-aminobutyric acid modulates antioxidant and osmoprotective systems in seedlings of Triticum aestivum cultivars differing in drought tolerance

Yu. E. Kolupaev1,2,3*, I. V. Shakhov1,3, A. I. Kokorev1,
L. Kryvoruchko2, T. O. Yastreb1,4

1Yuriev Plant Production Institute, National Academy of Agrarian Sciences of Ukraine, Kharkiv;
*e-mail: plant_biology@ukr.net;
2Poltava State Agrarian University, Poltava, Ukraine;
3State Biotechnological University, Kharkiv, Ukraine;
4Crop Research Institute, Prague, Czech Republic

Received: 28 August 2023; Revised: 30 September 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023

The stress-protective effects of plant neurotransmitters, including gamma-aminobutyric acid (GABA) have been intensively examined in recent years. However, studies on the GABA influence on stress protective systems in bread wheat cultivars with different drought adaptation strategies are still lacking. The aim of this work was to estimate the GABA effect on the state of antioxidant and osmoprotective systems in etiolated seedlings of two wheat cultivars differing significantly in drought tolerance, namely Doskonala (non-drought-resistant) and Tobak (drought-resistant) under model drought induced by PEG 6000. Two-day-old seedlings were transferred to 15% PEG 6000 and incubated for two days in the absence or presence of GABA. Treatment with 0.1 and 0.5 mM GABA significantly reduced the growth-inhibitory effect of PEG 6000 on the roots and shoots of both cultivars, but to a greater extent on those of non-resistant Doskonala. It was shown that GABA treatment reduced drought-induced accumulation of H2O2 and MDA, stabilized SOD and GPX activity, the level of sugars, anthocyanins and flavonoids in seedlings of both cultivars. Meanwhile GABA treatment enhanced the stress-induced increase in proline content in the Doskonala cultivar, but decreased it in the Tobak, completely prevented stress induced decrease in anthocyanins and flavonoids level in the Tobak and only partially in Doskonala cultivar. Thus, the stabilization of the stress-protective systems functioning in the wheat cultivars and variety-dependent differences in response to GABA were revealed.

The effect of L-glutamic acid and N-acetylcysteine administration on biochemical blood parameters in rats treated with CCl(4)

N. O. Salyha

Institute of Animal Biology NAAS of Ukraine, Lviv;
е-mail: ynosyt@yahoo.com

Received: 30 March 2023; Revised: 19 May 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023

A toxic organic substance CCl4 is a well known model compound for studying detoxification function of the liver and developing oxidative stress. The goal of the study was to estimate the effect of L-glutamic acid (L-Glu) and N-acetylcysteine (NAC) administration on rat blood parameters upon the toxic effects of CCl4. Experimental male Wistar rats were injected intraperitoneally with CCl4, the rats of CCl4/L‑Glu group were additionally injected with L-Glu (750 mg/kg), of CCl4/NAC group – with NAC (150 mg/kg), of CCl4/L-Glu/NAC group – with L-Glu (750 mg/kg) and NAC (150 mg/kg). The duration of the experiment was 24 h. Increased level of lipid peroxides, TBARS, triacylglycerols, cholesterol and decreased glutathione peroxidase, glutathione reductase, glutathione-S-transferase activity and GSH content were observed in the blood of the CCl4 treated animals compared to the control untreated group. When animals were additionally injected with L-Glu or L-Glu/NAC, the most of the studied indicators were shown to be close to the control level These results suggest that the mentioned above aminoacids attenuated CCl4-induced oxidative stress in the blood of rats.

Oxydative stress in type 2 diabetic patients: involvement of HIF-1 alpha AND mTOR genes expression

Y. A. Saenko1, O. O. Gonchar2*, I. M. Mankovska2,
T. I. Drevytska2, L. V. Bratus2, B. M. Mankovsky1,3

1SI “The Scientific and Practical Medical Center of Pediatric Cardiology and Cardiac Surgery
of the Ministry of Health of Ukraine”, Clinic for Adults, Kyiv;
2Department of Hypoxia, Bogomoletz Institute of Physiology,
National Academy of Sciences of Ukraine, Kyiv;
3Shupyk National Healthcare University of Ukraine, Kyiv;
*e-mail:olga.gonchar@i.ua

Received: 22 March 2023; Revised: 25 May 2023;
Accepted: 05 June 2023; Available on-line:  20 June 2023

Biochemical and genetic mechanisms of oxidative stress (OS) developing in the blood of patients with type 2 Diabetes mellitus (T2DM) were studied. Twenty patients with T2DM and 10 healthy persons participated in this study. Lipid peroxidation, the content of protein carbonyls and H2O2 production were measured in blood plasma and erythrocytes as OS biomarkers. Activity of SOD, catalase, and GPx as well as reduced glutathionе (GSH) level in plasma and erythrocytes were estimated. The gene expression of key regulators of oxygen and metabolic homeostasis (HIF-1α and mTOR) in leukocytes were studied. It was found a significant rise in TBARS and protein carbonyls content in plasma as well as H2O2 production in erythrocytes from patients with T2DM compared to control. The diabetic patients also demonstrated an increase in the SOD and catalase activity in plasma and significantly lower GSH content and GPx activity in erythrocytes compared to the healthy participants. The established marked inhibition of mTOR gene expression and the tendency to an increase in HIF-1α gene expression in leukocytes of patients with T2DM may serve as a protective mechanism which counteracts OS developing and oxidative cell damage.