Tag Archives: oxidative stress

Rhabdomyolysis attenuates activity of semicarbazide sensitive amine oxidase as the marker of nephropathy in diabetic rats

O. Hudkova*, I. Krysiuk, L. Drobot, N. Latyshko

Department of Cell Signaling, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: ogudkova@biohem.kiev.ua

Received: 22 December 2021; Accepted: 21 January 2022

Amine oxidases are involved in the progression of many diseases and their complications, including renal failure, due to the generation of the three toxic metabolites (H2O2, aldehydes, and ammonia) in the course of biogenic amines oxidative deamination. The participation of the first two products in kidney pathogenesis was confirmed, whereas the role of ammonia as a potential inducer of the nitrozative stress is not yet understood. The aim of the present study was to test how further intensification of oxidative stress would affect diabetes-mediated metabolic changes. For this purpose, a rat model of glycerol-induced rhabdomyolysis, as a source of powerful oxidative stress due to the release of labile Fe3+ from ruptured myocytes, on the background of streptozotocin-induced diabetes was used. The experimental animal groups were as follows: group 1 – ‘Control’, group 2 – ‘Diabetes’, group 3 – ‘Diabetes + rhabdomyolysis’. A multifold increase in semicarbazide sensitive amine oxidase (SSAO) activity in the kidney and blood, free radicals (FR), MetHb and 3-nitrotyrosine (3-NT) levels in the blood, as well as the emergence of HbNO in plasma and dinitrosyl iron complexes (DNICs) in the liver of animals in group 2 as compared to control were revealed. An additional increase in FR, HbNO levels in the blood, and DNICs in the liver of animals in the diabetes + rhabdomyolysis group as compared to the diabetes group, which correlated with the appearance of a large amount of Fe3+ in the blood of group 3 animals, was detected. Unexpectedly, we observed the positive regulatory effects in animals of the diabetes + rhabdomyolysis group, in particular, a decreased SSAO activity in the kidney and 3-NT level in plasma, as well as the normalization of activity of pro- and antioxidant enzymes in the blood and liver compared to animals of diabetes group. These consequences mediated by rhabdomyolysis may be the result of NO exclusion from the circulation due to the excessive formation of NO stable complexes in the blood and liver. The data obtained allow us to consider SSAO activity as a marker of renal failure in diabetes mellitus. In addition, we suggest a significant role of nitrosative stress in the development of pathology, and, therefore, recommend NO-traps in the complex treatment of diabetic complications.

Dietary protein defines stress resistance, oxidative damages and antioxidant defense system in Drosophila melanogaster

O. Strilbytska1*, A. Zayachkivska1, T. Strutynska1,
U. Semaniuk1, A. Vaiserman2, O. Lushchak1,3*

1Vasyl Stefanyk Precarpathian National University,
Department of Biochemistry and Biotechnology, Ivano-Frankivsk, Ukraine;
2D.F. Chebotarev Institute of Gerontology, NAMS, Kyiv, Ukraine;
3Research and Development Institute, Ivano-Frankivsk, Ukraine;
*e-mail: olya_b08@ukr.net or oleh.lushchak@pnu.edu.ua

Received: 06 April 2021; Accepted: 22 September 2021

Dietary interventions have been previously shown to influence lifespan in diverse model organisms. Manipulations with macronutrients content including protein and amino acids have a significant impact on various fitness and behavioral traits in the fruit fly Drosophila melanogaster. Therefore, we asked if yeast amount of the diet could influence stress resistance and antioxidant defense system in Drosophila. We examined the effects of four diets differing in the relative level of yeast, as a source of protein, on resistance to cold, heat, starvation and oxidative stress induced by menadione as well as activities of antioxidant enzymes and levels of oxidative stress markers. Protein restriction as well protein-enriched diet led to a reduction of survival under starvation and oxidative stress conditions. However, enhanced resistance to heat shock was affected by high yeast concentration in the diet. Also, protein-rich diets resulted in higher activity of antioxidant enzymes. Increased levels of protein thiols, low-molecule mass thiols, lipid peroxides in response to high yeast concentration in the diet were detected in females only. Thus, we can assume that consumption of a high protein diet could induce oxidative stress in fruit fly.

Metallothioneins involment in the pathogenesis of synovial tissue inflammation in rats with acute gonarthritis

T. R. Matskiv1,2, D. V. Lytkin3, S. K. Shebeko3, V. V. Khoma2,
V. V. Martyniuk2, L. L. Gnatyshyna1,2, O. B. Stoliar2*

1I. Horbachevsky Ternopil National Medical University, Department of General Chemistry, Ternopil, Ukraine;
2Ternopil Volodymyr Hnatiuk National Pedagogical University, Department of Chemistry and Methods its Teaching, Ternopil, Ukraine;
3National University of Pharmacy, Educational and Scientific Institute of Applied Pharmacy, Kharkiv, Ukraine;
*e-mail: Oksana.Stolyar@tnpu.edu.ua

Received: 02 June 2021; Accepted: 22 September 2021

Zinc (Zn) is involving in the suppressing of inflammation. However, its functionality in the knee joint under the gonarthritis (GA) is not elucidated. The aim of this study was to investigate the participation of Zn-buffering and stress responsive proteins metallothioneins (MTs) in the pathogenesis of the synovial tissues under the experimental acute GA. The inflammation was induced in rats by intra-articular administration of carrageenan. The concentrations of MTs total protein (MTSH), Zn-bound protein (Zn-MTs), total Zn concentration in the tissue, the indexes of oxidative stress and cholinesterase activity were determined. The level of sialic acids was indicated in the blood serum. The enhancing of sialic acids concentration by 42% and cholinesterase depletion confirmed the pathology. In the animals with GA, total level of Zn in the tissue was correspondent to control. However, the MTSH and Zn-MT levels were elevated (by 79 and 46% respectively). This disproportionate rate can be due to partial oxidation of thiols. The superoxide dismutase activity was elevated, radical scavenging activity and protein carbonylation were correspondent to control, but the levels of catalase, glutathione–S-transferase and glutathione  were decreased by 28-44%, and lipid peroxidation (TBARS) was increased by 59% compared to control group. Principal Component Analysis confirmed the strong interrelations between MTs and peroxide-related oxidative stress indexes. This preliminary study provides the basis for the understanding of the reason for Zn imbalance in the acute GA as the result of the impairment of thiol redox balance and proposes these biomarkers for the evaluation of knee joint pathologies.

Oxidative stress in rat heart mitochondria under a rotenone model of Parkinson’ disease: a corrective effect of capicor treatment

O. O. Gonchar*, O. O. Klymenko, T. I. Drevytska,
L. V. Bratus, I. M. Mankovska

Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: olga.gonchar@i.ua

Received: 22 March 2021; Accepted: 22 September 2021

Biochemical and genetic mechanisms of oxidative stress (OS) developing in rat heart mitochondria were studied in a rotenone model of Parkinson’s disease (PD), and the effect of Capicor (combination of meldonium dihydrate and gamma-butyrobetain dihydrate) on these mechanisms was evaluated. Experiments  were carried out on adult male Wistar rats: I – intact rats (control); II –with rotenone administration subcutaneously at dose 3 mg/kg per day along 2 weeks; III – with rotenone/Capicor administration: after rotenone intoxication, capicor was injected intraperitoneally at dose 50 mg/kg per day along following 2 weeks. As OS biomarkers, lipid peroxidation, protein oxidative modification, H2O2 production, the activity of MnSOD, GPx and glutathione pool indexes were measured. The PD-related genes Parkin (PARK2) and DJ-1 (PARK7) as well as MnSOD and DJ-1 protein expressions were detected. Rotenone intoxication increased the intensity of lipid peroxidation, protein oxidative modification, and H2O2 production. These events were accompanied by decreased in GSH content, GSH/GSSG ratio, and GPx activity. Increased ROS production and impaired antioxidant defenses could result from the established DJ-1 gene and DJ-1 protein deficiency. Capicor administration increased  the endogenous antioxidant defense, weakening the lipid peroxidation and oxidative modification of mitochondrial proteins. Capicor treatment led to an increase in GSH content and GSH/GSSG ratio in heart mitochondria that may serve as additional indicators of the OS intensity reducing. Capicor promoted overexpression of DJ-1 and PARK2 genes in the heart that may indicate a rise in mitophagy and a decrease in OS.

Protective effect of Atriplex halimus extract against benzene-induced haematotoxicity in rats

K. Zeghib1*, D. A. Boutlelis2, S. Menai3, M. Debouba4

1Department of chemistry, Faculty of exact sciences, University of El-Oued, El-Oued, Algeria;
2Department of Biology, Faculty of natural sciences and life, University of El-Oued, El-Oued, Algeria;
3The mother-child hospital (Bachir Bennacer) of El-Oued, El-Oued, Algeria;
4Higher Institute of Applied Biology of Medenine, University of Gabès, Tunisia;
*e-mail: zeghib-khaoula@univ-eloued.dz

Received: 24 December 2020; Accepted: 07 July 2021

Benzen (BZ) is a ubiquitous environmental pollutant with a toxic effect mainly aimed at the hematopoietic­ and immune systems. Atriplex halimus L. (Amaranthaceae) is a Mediterranean halophytic shrub traditionally used in North Africa as medicinal plant  for several therapeutic uses. The present study aimed to estimate the preventive and curative effects of Atriplex halimus L. (Ah) aqueous extract against BZ-induced hematotoxici­ty in rats. Analysis of the extract by the method of LC-MS revealed the presence of 7 vitamins, among which vitamin  C content was the highest. Adult rats were divided into five groups as follow: Group 1 received water (control); Group 2 received orally Ah aqueous extract (200 mg/kg) 3 days/week  for 15 weeks; Group 3 received BZ (100 mg/kg b.w) daily in drinking water for 15 weeks; Group 4 received concomitantly BZ (100 mg/kg) and  preventive treatment with Ah (200 mg/kg) for 15 weeks (AhP+BZ); Group 5 first received BZ (100 mg/kg) for 11 weeks and then curative treatment with Ah extract (300 mg/kg) daily for 30 days (BZ+AhC). It was shown that sub-chronic exposure to benzene induced leukopenia, lymphocytopenia, granulocytopenia and massive degeneration of the bone marrow tissue. The level of GSH and activity of GST and CAT were significantly lowered and the level of MDA was increased in the blood and bone marrow in rats of BZ-intoxicated group compared to the control rats. Administration of Ah extract recovered the bone marrow structure, dramatically decreased MDA content and increased GSH and CAT activity and GST level in the blood and bone marrow as compared with the indices in BZ-treated group. These observations demonstrate that curative and, to a lesser extent, preventive treatment with Atriplex halimus extract have therapeutic potential against hematotoxicity induced by benzene.

Sex dependent differences in oxidative stress in the heart of rats with type 2 diabetes

N. I. Gorbenko1*, O. Yu. Borikov2, O. V. Ivanova1, T. V. Kiprych1,
E. V. Taran1, T. I. Gopciy2, Т. S. Litvinova1

1SI “V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine”, Kharkiv;
2V.N. Karazin Kharkiv National University, Kharkov, Ukraine;.
*е-mail: Gorbenkonat58@ukr.net

Received: 17 September 2020; Accepted: 17 May 2021

Type 2 diabetes mellitus is known to double mortality from cardiovascular diseases (CVD), in which oxidative stress plays an important role. It is suggested that the impact of diabetes on CVD risk may vary depending on gender. The aim of the study was to assess oxidative stress parameters in the heart of 12 weeks old male and female Wistar rats with type 2 diabetes mellitus (T2DM) induced by high-calorie diet followed by intraperitoneal streptozotocin injections. The level of advanced oxidation protein products, superoxide dismutase, glutathione reductase and glutathione peroxidase activity in the isolated heart mitochondria and NADPH-oxidase and xanthine oxidase activity in the post-mitochondrial  supernatant fraction were determined. It was shown that T2DM induced more pronounced oxidative stress confirmed by the increased level of advanced oxidation protein products in the heart mitochondria of males than females. The data obtained indicate that the main reason of oxidative stress in the heart of diabetic males is the activation of non-mitochondrial  sources of reactive oxygen species. While in the heart of diabetic female rats it is the  decrease in antioxidant enzymes activity in mitochondria. These results justify the necessity of gender-specific therapy for the prevention and management of diabetic CVD.

Oxidative stress in the heart of rats exposed to acute intermittent hypobaric hypoxia

S. Dewi1*, M. Sadikin1, W. Mulyawan2

1Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia;
2Department of Aerophysiology, Lakespra Saryanto, Air Force Indonesian National Army, Jakarta, Indonesia;
*e-mail: syarifah.dewi@ui.ac.id

Received: 01 October 2020; Accepted: 17 May 2021

It is known that the altitude area causes hypoxic conditions due to the low oxygen partial pressure. This study was conducted to estimate oxidative stress indices in the heart tissue after Wister rats exposure to the acute intermittent hypobaric hypoxia. Hypobaric hypoxia exposure was simulated by keeping the rats in a hypobaric chamber for 1 min at 35,000 feet altitude. After that the altitude was gradually reduced to 30,000 and 25,000 feet and maitained for 5 min. 25 male Wistar rats were divided into control group and four treatment groups (I-IV), consisting of rats exposed 1, 2, 3 and 4 times to hypobaric hypoxia with a frequency once a week. The animals were removed from the experiment at the  height of 18,000 feet and the heart tissue was obtained. The carbonyl groups and  MDA levels and superoxide dismutase and  catalase activity were exami­ned in the supernatant of the heart tissue homogenate. In the samples of group I, the decrease  in catalase activity with a simultaneous notable increase in carbonyl groups level was observed compared to control. In the samples of groups III and IV, the carbonyl level normalized and the activity of  both antioxidant enzymes increased significantly. It was concluded that the increase of antioxidant enzymes activity can contribute to cardiac tissue adaptive response to acute hypobaric hypoxia exposure.

Oxidative stress suppression contributes to antiseizure action of axitinib and rapamycin in pentylenetetrazol-induced kindling

O. B. Poshyvak1*, O. R. Pinyazhko1,2, L. S. Godlevsky3

1Pharmacology Department, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
2Department of Civilization Diseases and Regenerative Medicine, WSIiZ, Rzeszow, Poland;
3Department of Biophysics, Informatics and Medical Devices, Odesa National Medical University, Odesa, Ukraine;
*e-mail: olesya.poshyvak@gmail.com

Received: 29 January 2021; Accepted: 23 April 2021

Rapamycin and axitinib block different kinases in signaling pathways such as PI3K-Akt-mTOR and BDNF-TrkB, respectively. Both have antiseizure and antioxidative actions, which justify studying the combined effects of these drugs upon seizures and oxidative stress in the chronic model of epilepsy. The investigation aimed to look for the combined effect of rapamycin and axitinib upon pentylenetetrazol (PTZ)-kindled seizures and oxidative stress. Experiments were performed on 300 two- to four-month-old Wistar male rats, which had been kindled daily with PTZ (35.0 mg/kg, i.p.). Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and glutathione (GSH) level were determined in brain tissues of kindled rats before and after the treatment. The analysis of antiseizure and antioxidative actions was performed using ED50 of rapamycin and axitinib, with their combined administration using graded dosages of ED50 of each drug. The median effective dose (ED50) for rapamycin and axitinib was 0.93 and 4.97 mg/kg, respectively. ED50 of rapamycin when combined with axitinib (2.0 mg/kg) was 0.60 mg/kg, which was reduced by 35.6% when compared with the ED50 administered alone (P < 0.05). The MDA level increased from 152.9±24.8 to 388.3±49.2 nmol/mg of protein (P < 0.05), while SOD activity reduced from 11.14±2.33 to 3.54±1.08 IU/mg of protein (P < 0.05) in brain tissues of the kindled rats. Combined treatment with rapamycin (0.56 mg/kg, i.p.) and axitinib (2.0 mg/kg, i.p.) resulted in a significant rise in SOD activity (11.09±1.86 IU/mg) and GSH level (7.32±1.34 µg/mg) when compared with the kindled rats (P < 0.05). Combined axitinib and rapamycin therapy have an antiepileptic and antioxidative effect on PTZ-kindled seizures.

Effect of N-acetyl cysteine on oxidative stress and Bax and Bcl2 expression in the kidney tissue of rats exposed to lead

M. Gholami1, A. B. Harchegani2, S. Saeedian3,
M. Owrang4, M. R. Parvizi1*

1Department of Physiology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran;
2Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
3Medical Genomic Research Center, Tehran Medicine Sciences Islamic Azad University, Tehran, Iran;
4Faculty of Medicine, Sari Branch, Islamic Azad University, Sari, Iran;
*e-mail: mparvizi@alumnus.tums.ac.ir

Received: 30 May 2020; Accepted: 17 December 2021

This study aimed to consider the lead-induced oxidative damage of the kidney of male rats and the role of antioxidant N-acetylcysteine (NAC) in preserving cells against Pb toxicity. Rats were randomly divided into five groups including G1 (control), G2 (single 70 mg/kg dose of Pb), G3 (continuous daily 2 mg/kg dosing of Pb for 4 weeks), G4 (single dose of Pb + 50 mg/kg NAC), and G5 (continuous daily dosing of Pb + 50 mg/kg NAC). The level of malonic dialdehyde (MDA) and total antioxidant capacity were measured spectrophotometrically.The level of Pb in  serum and kidney tissue was measured by atomic absorption spectroscopy. Expression of Bax and Bcl2 genes was estimated using RT-PCR.  It was shown that single and continuous exposure to Pb caused a considerable increase of Pb content in serum and kidney tissue of rats in G2 and G3 groups compared to other groups. NAC treatment significantly improved TAC values and decreased MDA values in the serum of rats exposed to Pb. Single and continuous Pb dosing caused a 3.9- and 13.1-fold increase in Bax expression and 1.5-fold and 2.1-fold decrease in Bcl2 expression in a kidney tissue respectively. The current study revealed that single and  especially continuous Pb exposure  was strongly associated with Pb accumulation, antioxidant depletion, oxidative stress and kidney cells apoptosis. NAC can help protect kidney tissue against Pb by elevating antioxidant capacity, mitigating oxidative stress and normalizing Bax and Bcl2 genes expression.

Protein intake and loss of proteostasis in the eldery

A. N. Kirana1, E. Prafiantini1, N. S. Hardiany2,3*

1Department of Nutrition, Faculty of Medicine, Universitas Indonesia – Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia;
2Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia;
3Center of Hypoxia and Oxidative Stress Studies, Faculty of Medicine, Universitas Indonesia;
*e-mail: novi.silvia@ui.ac.id

Received: 29 June 2020; Accepted: 17 December 2020

Ageing is a process of declining bodily function and a major risk factor of chronic diseases. The declining bodily function in ageing can cause loss of proteostasis (protein homeostasis), which is a balance between protein synthesis, folding, modification and degradation. For the elderly, adequate protein intake is necessary to prevent sarcopenia, frailty, fracture and osteoporosis as well as reduced resistance to infection. However, increasing the protein intake can enhance the risk of oxidized protein formation, loss of proteostasis and degenerative disorder occurrence. On the other hand, several studies show that protein restriction would increase longevity. The aim of this review was to explain the importance of determining the right amount and composition of protein intake for the elderly. Oxidative stress and molecular mechanism of proteostasis loss in ageing cells as well as its suppression pathway by protein restriction are discussed in this review.