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C(60) fullerene attenuates the signs of acute renal failure in rats under rhabdomyolysis due to inhibition of oxidative stress
O. Omelchuk1, S. Prylutska2, D. Nozdrenko3,
O. Motuziuk1,3, I. Vareniuk3, K. Bogutska3,
O. Vygovska4, А. Zholos3, Yu. Prylutskyy3*
1Lesya Ukrainka Volyn National University, Lutsk, Ukraine;
2National University of Life and Environmental Science of Ukraine, Kyiv, Ukraine;
3Taras Shevchenko National University of Kyiv, Ukraine;
*e-mail: prylut@ukr.net;
4Bogomolets National Medical University, Kyiv, Ukraine
Received: 14 August 2023; Revised: 18 September 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023
Rhabdomyolysis, as an acute stage of myopathy is known to be associated with the accumulation of muscle breakdown products, acute renal failure and oxidative stress. The goal of the study was to evaluate the effect of C60 fullerene as an antioxidant on kidney damage in the model of glycerol-induced rhabdomyolysis in rats. The study was conducted on male Wistar rats, divided into the following experimental groups: control animals, animals intramuscularly injected with glycerol in a doses of 5, 10 and 15 mg/kg and those intraperitoneally injected daily with C60 fullerene aqueous solution (C60FAS) in a dose of 1 or 2 mg/kg at 48 h after glycerol administration. Monitoring of the biochemical and morphological indicators was carried out on 3rd, 6th and 9th days of the experiment. A close correlation between the acute renal damage severity, increased creatinine and urea level, superoxide dismutase (SOD) and catalase (CAT) activity in the blood of rats was observed. It was shown that in rats which received 2 mg/kg of C60FAS the renal glomeruli size and necrosis manifestations were attenuated, whereas SOD and CAT activity in the blood was significantly decreased. The results obtained may be useful for developing approaches to the treatment of pathological conditions of the muscular system caused by rhabdomyolysis and associated oxidative stress.
Bioenergetic functions of mitochondria in liver, pancreatic acinar cells, and sperm cells of rats fed short-term high-fat or high-fat high-sugar diets
B. V. Manko1*, N. M. Kozopas1,2, H. M. Mazur1,
A. М. Voityk1, B. O. Manko1, V. V. Manko1
1Ivan Franko National University of Lviv,
Department of Human and Animal Physiology, Lviv, Ukraine;
2Danylo Halytsky Lviv National Medical University,
Department of Clinical Laboratory Diagnostics, Lviv, Ukraine;
*e-mail: bohdan.manko.ablb@lnu.edu.ua
Received: 26 September 2023; Revised: 23 October 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023
An unhealthy diet often is a cause of obesity, chronic inflammation, and metabolic disruption in multiple organs. However, the direct influence of elevated lipid or sugar consumption on liver, pancreatic, and sperm mitochondria is not well understood. The aim of the study was to investigate the functional activity of mitochondria of liver, pancreatic acinar cells, and sperm cells in rats on a short-term (7 weeks) diet with high fat or high fat and high sugar content. Male Wistar rats were on a basic, high-fat or high-fat high-sugar diet for 7 weeks. At the end of the experiment, visceral fat mass, blood glucose and lipids were measured. Mitochondrial functional activity was evaluated with oxygen consumption assay. In isolated pancreatic acinar cells, NAD(P)H autofluorescence and mitochondrial membrane potential were also studied. No difference in body mass was observed between the 3 groups at the end of the experiment. Visceral fat mass was slightly but significantly elevated in rats on a high-fat high-sugar diet. Both diets did not affect plasma glucose or triglyceride levels but caused a modest elevation of total plasma cholesterol. Respiration and oxidative phosphorylation of isolated liver mitochondria were not affected by any experimental diet. In pancreatic acinar cells, a high-fat diet caused a significant decrease of basal respiration by ~15%, but no effects were observed on the maximal rate of uncoupled respiration, mitochondrial membrane potential, or NAD(P)H autofluorescence. In these cells, a ketone body 3-hydroxybutyrate caused elevation of uncoupled respiration and NAD(P)H level irrespectively of the diet. Diets did not cause any change in sperm concentration, viability or motility. Surprisingly, in animals on a high-fat high-sugar diet, a significant increase in both basal and maximal respiration of sperm cells was observed. Collectively, these data show that while the elevated fat and sugar content in the diet does not cause significant obesity, no detrimental effects on mitochondria of the liver, pancreas, and sperm cells are observed.
Novel biochemical markers for the prediction of renal injury in beta-thalassemia major pediatric patients
A. J. Shwayel1*, A. M. Jewad1, M. Q. Abdulsattar2
1Department of Medical Laboratory Technology, Health and Medical Technical College,
Southern Technical University, Basrah, Iraq;
2Thi-Qar Health Directorate, Iraq;
*е-mail: ameeralzaidy6@gmail.com
Received: 07 June 2023; Revised: 14 August 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023
Beta-thalassemia major is a severe inherited disorder characterized by inadequate production of hemoglobin beta chains, ineffective erythropoiesis, chronic hemolysis and necessitates lifelong transfusions, which lead to iron overload. The disease manifests itself in early childhood and persists throughout an individual’s life with a high risk of developing renal impairment, which cannot be reliably determined using routine markers. The objective of this research was to apply biomarkers to the evaluation of renal injury in pediatric patients within the age range of 1–14 years diagnosed with beta-thalassemia major. In the case-control study, the blood samples obtained in the Genetic Hematology Center in Thi-Qar Iraq Province were used: 60 samples from healthy individuals and 60 samples from the patients with beta-thalassemia, subdivided into 1-7 and 8-14 years old groups. The levels of hemoglobin, ferritin, creatinine and potassium were estimated with standard tests, enzyme-linked immunoassay was used to determine the level of neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) as novel markers of tubular and glomerular dysfunctions. The study revealed a statistically significant decrease in hemoglobin, serum potassium levels and an increase in ferritin, NGAL and β2M levels in the patients from both groups compared to controls and elevation of creatinine level in the 8–14-year-old group. It was concluded that NGAL and β2M levels may be considered indicators for the early diagnosis of renal injury in pediatric patients with beta-thalassemia, as these biomarkers exhibit elevated levels before an increase in creatinine is observed.
Assessment of urinary podocalyxin as a biomarker of early diagnosis of hypertensive nephropathy
I. Kostovska*, K. Tosheska-Trajkovska, D. Labudovic,
S. Cekovska, O. Kostovski, G. Spasovski
Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia;
*e-mail: irenakostovska22@yahoo.com
Received: 31 August 2023; Revised: 28 September 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023
Chronically high blood pressure-related kidney injury is known as hypertensive nephropathy (HN). Podocyte damage in the pathogenesis of this disease can result in the release of the sialoglycoprotein podocalyxin into the urine, so podocalyxin may be useful in the early diagnosis of HN. The purpose of the study was to examine the relationships between urine podocalyxin level and clinical and biochemical parameters in individuals with HN and to assess the diagnostic utility of urinary podocalyxin as an early marker of HN. Participants (114 individuals) were enrolled in this cross-sectional study, including 30 healthy controls and 84 patients with clinically proven chronic hypertension (CH). Biochemical tests were performed on the blood samples. Urinary microalbumin and creatinine levels were measured using immunoturbidimetric and spectrophotometric methods, respectively; urinary podocalyxin level was estimated with ELISA. All CH patients were classified into subgroups according to urine microalbumin/creatinine ratio (UM/CR) and the stage of chronic kidney disease (CKD). The results obtained showed that urinary podocalyxin level was significantly increased in both UM/CR and CKD staging subgroups compared with the healthy control group. A gradual increase in urinary podocalyxin level with CKD stage, especially in IV and V stages, and the higher sensitivity of urinary podocalyxin as compared to UM/CR ratio in early detection of HN was demonstrated. It was concluded that urinary podocalyxin may be an important and highly sensitive marker for early diagnosis of hypertensive nephropathy in patients with chronic hypertension.
Assessing the relationship between organ function test results and COVID-19 severity
A. K. Yadav1, M. K. Mishra2*, S. Prasad3, S. Singh4
1Department of Biochemistry, Heritage Institute of Medical Science, Varanasi, U.P., India;
2Department of Biochemistry, GMERS Medical College & Hospital, Vadnagar, Gujarat, India;
3Department of Biochemistry, K. J. Somaiya Medical College & Research Centre, Mumbai, India;
4Department of Microbiology, Integral Institute of Medical Science and Research, Lucknow, U.P., India;
*e-mail: mritunjaymishra007@gmail.com
Received: 25 July 2023; Revised: 12 October 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023
A number of recent reports have indicated the association of COVID-19 with multiple organ failure and the need to clarify the relationship between organ testing parameters and disease progression. Therefore, this study aimed to determine the degree of abnormal organ function test parameters and its correlation with COVID-19 severity. A cross-sectional study was conducted among COVID-19 patients admitted at Sanaka hospital, India, from August to September 2020. A total of 100 qRT-PCR-confirmed COVID-19 patients divided into groups with mild or severe cases were enrolled. The data from venous blood samples for liver, renal, cardiac and inflammatory test parameters were included from the Sanaka hospital laboratory database. Biochemical prognostic tests were carried out using a clinical automated ERBA analyzer, cardiac markers were estimated with Enzyme Linked Fluorescent Assay. The Pearson correlation analysis was used to analyze the data. Aspartate/Alanine aminotransferases and alkaline phosphatase activity, creatinine, urea and troponin levels were higher in the confirmed positive cases of COVID-19. Significantly higher levels of troponin, D-dimer and C reactive protein (CRP) were found in patients with severe COVID form compared to a mild one. A strong positive correlation between elevated D-dimer and Ferritin with CRP level was revealed in this group of patients. It was concluded that the positive relationship between serum D-dimer, ferritin levels and CRP level in patients can be considered a stable indicator of disease severity.
A new affine inhibitor of sodium pump thiacalix[4]arene С-1193 increases the intracellular concentration of Ca ions and modifies myometrium contractility
Т. О. Veklich1*, S. О. Cherenok2, О. V. Tsymbalyuk3, О. A. Shkrabak1,
S. O. Karakhim1, A. I. Selihova2, V. І. Kalchenko2, S. O. Kosterin1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: veklich@biochem.kiev.ua;
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
3Educational and Scientific Institute of High Technologies,
Taras Shevchenko National University of Kyiv, Ukraine
Received: 16 June 2023; Revised: 31 September 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023
The methods of enzymatic and kinetic analysis were used to demonstrate that thiacalix[4]arene-bis-hydroxymethylphosphonic acid С-1193 had the inhibitory effect (І0.5 = 42.1 ± 0.6 nM) on Na+,K+-ATPase activity in the plasma membrane of myometrium cells with no effect on the relative activity of other ATPases localized in this subcellular structure. The method of confocal microscopy and Са2+-sensitive fluorescent probe fluo-4 were used to demonstrate that thiacalix[4]arene С-1193 increased the intracellular concentration of Ca ions in the immobilized uterine myocytes. The tenzometric studies proved that С-1193 (10 and 100 μМ) increased the isometric phasic contractions, induced via the paths of both electromechanical (depolarization with high-potassium solution) and pharmacomechanical (application of uterotonic hormone oxytocin, neurotransmitter acetylcholine or selective agonist of muscarinic acetylcholine receptors cevimeline) coupling. Application of thiacalix[4]arene С-1193 as a selective and effective inhibitor of Nа+,K+-ATPase may be useful both for studyng the regulation of ion homeostasis in smooth muscle cells and creation of new uterotonics based on the calixarene core.
Undecylenic acid and N,N-dibutylundecenamide as effective antibacterials against antibiotic-resistant strains
Y. D. Startseva*, D. M. Hodyna, I. V. Semenyuta,
O. P. Tarasyuk, S. P. Rogalsky, L. O. Metelytsia
V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: startseva1991@gmail.com
Received: 25 April 2023; Revised: 03 July 2023;
Accepted: 7 September 2023; Available on-line: 12 September 2023
Evaluation of undecylenic acid (UA) and its tertiary amide N,N-dibutylundecenamide (DBUA) activity in vitro against the standard and antibiotic-resistant Escherichia coli and Staphylococcus aureus strains was carried out. The antibacterial potential of the acid and its amide at 2.5 and 5.0 μM concentration both against gram-positive bacteria (S. aureus) and gram-negative (E. coli) cultures was confirmed by monitoring the diameter of the bacterial growth inhibition zones. The docking study identified methionine aminopeptidase (MAP) as the most energy-favorable potential biotarget associated with the drug resistance of E. coli and S. aureus with a binding energy in the range from -8.0 to -8.5 kcal/mol. The ligands complexation was due to the formation of hydrogen bonds with ASP108, HIS171, HIS178, GLU204, GLU235, HIS76, ASP104, GLU233, ASP93 and metal-acceptor interactions with Co2+. Overall, the results indicated that UA and DBUA activity against antibiotic-resistant strains creates prospects for the development of new antibacterial formulations.