Tag Archives: oxidative stress
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.
A vicious circle between oxidative stress and cytokine storm in acute respiratory distress syndrome pathogenesis at COVID-19 infection
G. H. Meftahi1, Z. Bahari1,2, Z. Jangravi3,4*, M. Iman3,5
1Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;
2Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran;
3Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;
4Department of Biochemistry, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran;
5Department of Pharmaceutics, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran;
*e-mail: jangraviz89@gmail.com
Received: 31 August 2020; Accepted: 17 December 2020
In early December 2019, the pandemic of coronavirus disease 2019 (COVID-19) began in Wuhan City, Hubei Province, China. Since then, it has propagated rapidly and turned into a major global crisis due to the high virus spreading. Acute respiratory distress syndrome (ARDS) is considered as a defining cause of the death cases. Cytokine storm and oxidative stress are the main players of ARDS development during respiratory virus infections. In this review, we discussed molecular mechanisms of a fatal vicious circle between oxidative stress and cytokine storm during COVID-19 infection. We also described how aging can inflame the vicious circle.
Effect of glutamic acid and cysteine on oxidative stress markers in rats
N. O. Salyha
Institute of Animal Biology, National Academy of Agrarian Sciences of Ukraine, Lviv;
е-mail: ynosyt@yahoo.com
Received: 7 May 2020; Accepted: 13 November 2020
Epinephrine (EPI) surges is known to be associated with stress induction and raising risk of heart strokes. The search for effective, nontoxic substances with antioxidative effects has been intensified in recent years. We focused our attention on two amino acids: L-glutamic acid (Glu) and L-cysteine (Cys). Our goal was to compare the effects of Glu, Cys and Glu in combination with Cys intraperitoneal administration on the antioxidant system indicators and the content of lipid peroxidation products in myocardium and spleen tissues of rats subjected to experimental EPI-induced stress. Rats were divided into five groups: EPI, EPI/Glu, EPI/Glu/Cys, EPI/Cys and control. The reduced glutathione (GSH) and TBA-active products level, glutathione peroxidase (GPx,), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH) activity in tissues were measured. Our results indicate that epinephrine-induced stress increased the content of the lipid peroxidation products in myocardium and reduced the level of GSH in myocardium and spleen tissues of rats. Increasing of GPx activity in spleen only stressed animals were observed, while significantly lowered the GPx activity in groups of rats treated with amino acids (Glu, Glu/Cys, Cys). The obtained results suggest that the GR activity was significantly inhibited by stress in all investigated groups in spleen and epinephrine-induced rats and EPI/Cys groups of rats in myocardium. In rats treated with amino acids (particularly, Glu and Glu/Cys groups), we observed no significant difference in studied parameters. Our results indicate that application of Glu, Cys alone or in combination can increase GSH content in both studied tissues and activity of some antioxidative enzymes, and thus partially mitigated of epinephrine-induced stress in rats.
Oxidative stress regulation in the yeast Ogataea polymorpha producer of human α-synuclein
N. V. Hrushanyk1, O. V. Stasyk2, O. G. Stasyk1*
1Ivan Franko National University of Lviv, Ukraine;
2Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
*e-mail: olenastasyk@gmail.com
Received: 02 March 2020; Accepted: 25 June 2020
In this study we analyzed how exogenous glucose levels affect enzymatic and non-enzymatic antioxidant defense systems and markers of oxidative stress in cells of the methylotrophic yeast Ogataea polymorpha producing recombinant human α-synuclein, implicated in pathogenesis of neurodegenerative Parkinson’s disease (PD). We found that glucose depletion up-induced activity of antioxidant enzymes superoxide dismutase, and catalase, and increased content of reduced and oxidized glutathione in the cells cultivated in the medium with 0.1% glucose, as compared to physiological growth condition (1% glucose-containing medium). In addition, low glucose concentration in the medium upregulated content of proteins carbonyl groups and of products of lipid peroxidation. Notably, the shift in the equilibrium toward pro-oxidant changes was similar for recombinant α-synuclein producer and parental wild-type strain. Thus, glucose limitation leads to the overproduction of reactive oxygen species in the methylotrophic yeast cells independently of the recombinant human α-synuclein production.
Effects of ethylthiosulfanylate and chromium (VI) on the state of pro/antioxidant system in rat liver
B. І. Kotyk1, R. Ya. Iskra1, O. M. Slivinska1, N. M. Liubas1,
A. Z. Pylypets1, V. I. Lubenets2, V. I. Pryimych3
1Institute of Animal Biology, NAAS of Ukraine, Lviv;
2Lviv Polytechnic National University, Ukraine;
3Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine;
e-mail: kicyniabo@gmail.com
Received: 04 April 2020; Accepted: 25 June 2020
Ethylthiosulfanylate is alkyl ester of thiosulfoacid and belongs to the class of thiosulfonate compounds. Structurally, thiosulfonates are synthetic analogues of natural phytoncides. It is known that, natural organic sulfur-containing compounds are characterized by antioxidant and detoxification properties against heavy metals toxicity. Therefore, the purpose of the study was to investigate the influence of ethylthiosulfanylate, as a synthetic analogue of natural phytoncides, on the state of the pro/antioxidant system in the liver of laboratory rats exposed to Cr(VI). It was found that ethylthiosulfanylate exposure at a dose 100 mg/kg body weight daily for 14 days led to a decrease in the intensity of increasing of the lipid hydroperoxides (LHP) content in the rat liver caused by Cr(VI) action. In addition, ethylthiosulfanylate pretreatment prevented depletion of reduced glutathione (GSH) pool under the action of potassium dichromate oxidative stress and performed the accumulation of cellular GSH in rat liver.
Profiling of metabolic biomarkers in the serum of prostate cancer patients
F. Ali1, S. Akram1, S. Niaz1,2, N. Wajid1
1Institute of Molecular Biology and Biotechnology (IMBB) & Centre for Research In Molecular Medicine (CRIMM), The University of Lahore, Raiwind Road Lahore, Pakistan;
2Social Security Hospital Multan Chungi, Multan Road, Lahore;
e-mail: Fatima.ali@imbb.uol.edu.pk; fatemei.ali@gmail.com
Received: 26 July 2019; Accepted: 29 November 2019
Prostate cancer (PCa) is the major cause of the death of men population globally. Multiple factors are involved in the initiation and progression of PCa. This study aimed to evaluate different metabolic parameters in the serum of PCa patients. Males of 50 years and above age with the recent diagnosis of PCa (digital rectal examination, and elevated serum prostate-specific antigen (PSA) level) were included in the study. Glucose and serum electrolytes level, lactate dehydrogenase activity, parameters of lipid metabolism and liver and kidney functioning were measured on a fully automated analyzer using standard reagent kits. Oxidative stress was evaluated by measuring MDA, CAT, GSH, and SOD in serum. Detection of C-reactive protein (CRP), insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF) was performed by immunoassay. It was shown that serum glucose and HDL levels were lower while total cholesterol, LDL and triglyceride levels were significantly higher in PCa group than in the control group. PCa patients had an elevated level of liver and kidney functional markers. Comparison of the oxidative stress markers in patient and control groups showed significant difference. It was detected that serum levels of CRP, IGF-1 and VEGF were significantly higher in PCa group, compared the control to group (P < 0.05). Low level of glucose and dyslipidemia indices in prostate cancer patients indicated metabolic changes and demonstrated the importance of multiple parameters analysis (free PSA, dyslipidemia, VEGF, IGF-1, CRP, and oxidative stress markers) for early PCa diagnostics.