Category Archives: Uncategorized
Diazepinone effect on liver tissue respiration and serum lipid content in rats with a rotenone model of Parkinson’s disease
L. Ya. Shtanova1,2*, P. I. Yanchuk1, S. P. Vesеlsky1,
O. V. Tsymbalyuk1, T. V. Vovkun2, V. S. Moskvina2, O. V. Shablykina2,
S. L. Bogza2, V. N. Baban1, A. A. Kravchenko3, V. P. Khilya2
1Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
2Taras Shevchenko National University of Kyiv, Ukraine;
3Chuiko Institute of Surface Chemistry, National Academy of Sciences, Kyiv;
*e-mail: shtanova@ukr.net
Received: 5 March 2020; Accepted: 13 November 2020
Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disorder. Accumulation of α-synuclein aggregates, oxidative stress, mitochondrial dysfunction and lipid metabolism disturbance are thought to be the key violations at PD pathogenesis. Despite long-time research the causes of PD occurrence are not yet clear. We investigated the influence of diazepinon, a new derivative of benzodiazepine, on liver tissue respiration (LTR), serum lipid content and behavioral parameters of rats with modeled PD induced by intraperitoneal injections of 2.0 mg/kg rotenone (ROT) within 28 days. LTR was assessed using the polarograph LP-9. Blood samples for biochemical analysis were collected from the inferior vena cava. The behavioral parameters of rats were studied by the open field test. We showed that in rats with ROT – induced PD the coefficient of liver oxygen consumption was decreased by 33.5% (P < 0.001), the serum content of phospholipids, cholesterol, cholesterol esters, free fatty acids and triglycerides was reduced by 21.4% (P < 0.001), 28.8% (P < 0.001), 26.8% (P < 0.001), 30.3% (P < 0.01) and 41.5% (P < 0.001) respectively and the motor disorders were detected. Diazepinone application resulted in a full recovery of LTR, serum concentration of phospholipids, partial recovery of serum free fatty acids and triglycerides content and significant improvement of motor behavior. However diazepinone did not affect the reduced concentration of cholesterol and cholesterol esters in the serum of rats with simulated PD.
The content of pro-inflammatory cytokines IL-1β, IL-6, IL-17A and TNFα in the blood of patients with type 2 diabetes after therapy with metformin
K. P. Zak*, O. V. Furmanova, V. V. Popova, Ya. A. Sayenko
SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of National Academia of Medical Sciences of Ukraine”, Kyiv;
*e-mail: kpzak2017@gmail.com
Received: 28 February 2020; Accepted: 13 November 2020
Currently the world society is extremely worried about the global increase in the number of patients with diabetes on our planet. Annually 4 million people die of this disease, and the cost of its treatment reaches trillions of dollars. A new highly effective oral antidiabetic drug metformin (1,1-dimethylbiguanide hydrochloride) is one of the most common hypoglycemic remedies currently prescribed for the first-line treatment of patients with type 2 diabetes (T2D). However, the mechanism of its curative effect is still not clear. The results of our study showed that metformin treatment of patients with newly diagnosed T2D was followed by pronounced normalization of the increased levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-17A and TNFα), inflammation indexes and lymphocyte’s immunophenotype. The obtained data confirm the existing hypothesis about the inflammatory nature of T2D and indicate that the immune system, in particular proinflammatory cytokines, plays a significant role in the mechanism of the curative effect of metformin at T2D.
Autoantibodies to myelin basic protein and histone H1 as immune biomarkers of neuropsychological disorders in patients with multiple sclerosis
S. Ya. Kyryliuk1, T. I. Nehrych1, N. K. Svyrydova2,
Ye. O. Trufanov2, R. S. Stoika3, Yu. Ya. Kit3
1Danylo Halytsky Lviv National Medical University, Ukraine;
2Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine;
3Institute of Cell Biology National Academy of Sciences of Ukraine, Lviv;
e-mail: sinitska@ukr.net
Received: 15 April 2020; Accepted: 13 November 2020
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with different disorders of neurological and higher cortical functions. It is important to identify biomarkers that can control the dynamics of neuropsychological changes and predict the progression of this process. The aim of the study was to investigate the pathogenic and clinical significance of serum autoantibodies to the myelin basic protein (MBP) and histone H1 in the occurrence of neurological and neuropsychological disorders in patients with MS. Fifty-five patients diagnosed for MS were examined. A general clinical and neurological examination, determination of cognitive status, depression level and the content of autoantibodies to histone H1 and MBP in the blood serum were conducted. Blood serum samples of 20 healthy volunteers were used in control. The serum of patients with MS was shown to contain antibodies of IgG class to MBP and histone H1. The level of anti-histone H1 IgG-antibodies in blood serum of MS patients was found to be higher compared with the level of anti-MBP IgG-antibodies (P < 0.05). Increased levels of anti-MBP antibodies correlated with the severity of trunk ataxia, impaired conceptualization, and mood. High level of anti-histone H1 antibodies correlated with the severity of paresis, trunk ataxia, impaired conceptualization, semantic language, and mood. Determination of the level of anti-histone H1 antibodies in blood serum of patients with MS might serve as a biomarker of inflammatory and, probably, of the neurodegenerative processes of this disease and determine the dynamics of clinical course of the MS. Anti-MBP antibodies play an important role in the pathogenesis of the MS and are an additional marker of the severity of the clinical course of neurological and some neuropsychological disorders.
Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes
T. S. Vatseba1*, L. K. Sokolova2, V. M. Pushkarev2,
O. I. Kovzun2, B. B. Guda2, V. V. Pushkarev2,
M. D. Tronko2, N. V. Skrypnyk1, L. M. Zaiats1
1Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine;
2SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv;
*e-mail: tamara.vatseba@gmail.com
Received: 17 April 2020; Accepted: 13 November 2020
Modern research shows that patients with diabetes mellitus have an increased risk of cancer. PI3K/Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. The aim of this study was to determine the state of РІ3K/Akt/mTORC1/p70S6K signaling cascade activity in peripheral mononuclear blood cells (PBMC) of patients with type 2 diabetes (T2D) relatively to the insulin and insulin-like growth factor (IGF-1) concentrations in blood plasma. Enzyme-linked immunosorbent assay was used to examine the levels of insulin and IGF-1 in blood plasma as well as the content of phosphorylated forms of Akt (Ser473), PRAS40 (Thr246), and p70S6K (Thr389) in PMBC. It was shown that in the blood plasma of patients with T2D the levels of insulin and IGF-1 were increased. Phosphorylation and activation of Akt by the mTORC2 protein kinase complex was not observed. At the same time, the relative degree of phosphorylation of mTORC1 inhibitor, PRAS40, and its substrate, p70S6K, was higher in PMBC of T2D patients in comparison with control values. These data suggest that phosphoinositide-dependent protein kinase 1 (PDK1) and, possibly, mitogen-activated protein kinase (MAPK) could mediate the effects of IGF-1 on Akt activation under type 2 diabetes.
Protective effects of hexane fraction of Costus afer leaves against sodium arsenite-induced hepatotoxicity and nephrotoxicity in male albino wistar rats
G. N. Anyasor*, O. O. Aramide, O. S. Shokunbi
Department of Biochemistry, School of Basic Medical Sciences,
Benjamin S. Carson (Snr.) College of Health and Medical Sciences, Babcock University,
Ilishan-Remo, Ogun State, Nigeria;
*e-mail: anyasorg@babcock.edu.ng
Received: 13 July 2020; Accepted: 13 November 2020
Arsenite is a toxic metallic pollutant known to cause hepatotoxic and nephrotoxic injuries. Costus afer Ker Gawl. is an indigenous medicinal plant used as therapy for numerous tissue disorders. Thus, this study investigated the protective potential of C. afer hexane leaf fraction (CALHF) on sodium arsenite-induced hepatic and renal injuries in albino rats. Twenty-five male albino rats were randomly distributed into five groups of five rats each. Group 1: rats administered orally with 0.5 ml of 0.9% saline; Group 2: untreated rats induced with 5 mg/kg body weight (b.w.) sodium arsenite (i.p.); Group 3: rats induced with sodium arsenite and treated with 10 mg/kg b.w. silymarin (hepatoprotective drug); Group 4 and 5: rats induced with sodium arsenite and treated with 100 and 200 mg/kg b.w. CALHF, respectively. CALHF was orally administered daily, while sodium arsenite was administered every 48 hours for 14 days. Thereafter, rats were sacrificed, blood was collected to estimate hepatic and nephrotic functions. Hepatic and renal function tests showed that 100 and 200 mg/kg CALHF and 10 mg/kg silymarin treated animals had significantly reduced (P < 0.05) plasma alanine aminotransferase, aspartate aminotransferase, creatinine and urea levels, when compared with those of untreated animals. C. afer hexane leaf fraction exhibited hepatoprotective and nephroprotective effects against sodium arsenite induced toxicity in rats.
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.
Functional activity of permeability transition pore in energized and deenergized rat liver mitochondria
O. V. Akopova*, L. I. Kolchinskaya, V. I. Nosar
Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: ov_akopova@ukr.net
Received: 15 June 2020; Accepted: 13 November 2020
Permeability transition pore (mPTP) opening was studied under energized and deenergized conditions in rat liver mitochondria, and the effect of membrane depolarization on mPTP activity was evaluated. To assess mPTP activity, cyclosporine-sensitive swelling and cyclosporine sensitive Ca2+ efflux from mitochondria was studied using light absorbance techniques. In energized mitochondria, mPTP opening in sub-conductance states, at [Ca2+] ≤ Ka, contributed positively to the rate of respiration, without affecting ΔΨm. Threshold Ca2+ concentrations were found, which excess resulted in fast mitochondrial depolarization upon mPTP opening. An estimate of mPTP activity by cyclosporine-sensitive Ca2+ transport under energized and deenergized conditions have shown that membrane depolarization by protonophore CCCP essentially increased initial rate (V0), at simultaneous decrease of the half-time (t1/2) of Ca2+ efflux, which indicated mPTP activation, as compared to energized mitochondria. However, only partial release of Ca2+ via mPTP upon membrane depolarization was observed. With the use of selective blockers of Ca2+ uniporter and mPTP, ruthenium red (RR) and cyclosporine A (CsA), partial contribution of Ca2+ uniporter and mPTP in Ca2+ transport was found. “Titration” of Ca2+ transport by adding RR at different times from the onset of depolarization showed that depolarization dramatically reduced “life span” of mPTP as compared to energized mitochondria, which agreed with the kinetic characteristics of CsA-sensitive Ca2+ transport after the abolition of ΔΨm. Ca2+ added from the outer side of mitochondrial membrane produced dual effect on mPTP activity: activation at the onset of depolarization, but consequent promotion of mPTP closure. Based on the experiments, it was concluded that mitochondrial energization was required for prolonged mPTP functioning in sub-conductance states, whereas membrane depolarization promoted the transition of mPTP to inactive state during calcium release from mitochondria.