Maria Zhelyazkova-Savova
@mu-varna.bg
Medical University Varna, Department of preclinical and clinical pharmacology and therapeutics
Medical University Varna
EDUCATION
Higher medical education MD - 1977
Specialty in Pharmacology - 1984
Specialty in Clinical Pharmacology - 2001
PhD - 2001
RESEARCH, TEACHING, or OTHER INTERESTS
Pharmacology (medical), Behavioral Neuroscience, General Pharmacology, Toxicology and Pharmaceutics, Endocrine and Autonomic Systems
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
M. Reyzov, M. Eftimov, S. Gancheva, M. Todorova, M. Zhelyazkova-Savova, M. Tzaneva, and S. Valcheva-Kuzmanova
Akademiai Kiado Zrt.
Abstract Metabolic syndrome (MS) is a serious health condition. The purpose of this study was to investigate the effects of polyphenol-rich Aronia melanocarpa fruit juice (AMFJ) on glucose tolerance, triglyceride levels, and adipose tissue in rats with MS induced by high-fat high-fructose (HFHF) diet. Fifty rats were allocated in 5 groups: control, MS, MS+AMFJ2.5, MS+AMFJ5, and MS+AMFJ10. In the course of 10 weeks, the control group was on a regular rat diet while the other groups received HFHF diet. During the experiment, control and MS groups were treated daily orally with distilled water (10.0 mL kg−1) and the other three groups – with AMFJ at doses of 2.5, 5.0, and 10.0 mL kg−1, respectively. In MS rats, glucose intolerance, hypertriglyceridemia, visceral obesity, and increased adipocyte size were observed. In AMFJ-treated groups, the serum glucose and triglycerides, as well as visceral fat and adipocyte size decreased significantly and did not differ from those of the control group. AMFJ at doses 2.5 and 5.0 mL kg−1 showed an anti-apoptotic activity in adipocytes, while at the dose of 10 mL kg−1 a pro-apoptotic effect was detected. In conclusion, AMFJ could antagonise most of the negative consequences of HFHF diet on carbohydrate and lipid metabolism in a rat MS model.
V. Kirkov, R. Zlatanova-Velikova, A. Vodenicharova, and N. Leventi
Walter de Gruyter GmbH
Abstract Providing a good quality in higher education should be the result of the interaction between the academic team, the students and the institutional learning environment. The quality is guaranteed by the learning environment in which the content of the programs and training opportunities is appropriate for the particular purpose. Aim: To study the organization, quality, consistency and satisfaction in practical training. Materials and Methods: This article presents and analyzes the results of a survey by medical graduates about their assessment of the organization and quality of training during the undergraduate internship. Results: The results show that the practical training of medical graduates is generally at a very high level, according to the indicators, examined in our study. Conclusion: More efforts in improving quality of education are welcome.
Maria D. Zhelyazkova‐Savova, Yoto T. Yotov, Miglena N. Nikolova, Neshe F. Nazifova‐Tasinova, Deyana G. Vankova, Atanas A. Atanasov, and Bistra Tz. Galunska
Wiley
The present cross‐sectional clinical study aimed to examine the connection between statin exposure, coronary artery calcification (CAC), and vitamin K‐dependent proteins (VKDPs) in patients with cardiovascular (CV) conditions. Two groups of patients were studied: patients with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were also split into statin users and non‐users. The following VKDPs were measured in plasma: uncarboxylated Matrix Gla‐protein (ucMGP), undercarboxylated (ucOC), and carboxylated osteocalcin (cOC), Gla‐rich protein (GRP). CAC score (CACS) was determined by multislice computed tomography. Among all the participants in the study, CACS was more pronounced in statin users compared to non‐users; the same was found also among the CVD patients and among the controls. While the levels of ucMGP and GRP did not differ between statin users and non‐users, ucOC and ucOC/cOC were significantly elevated in statin users, indicating vitamin K deficiency. There was a positive correlation between the levels of ucOC and CACS in the entire population and in the group of statin users, but not in statin non‐users. No association was found between ucMGP or GRP and CACS. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists (VKAs). Our results are in agreement with the existing evidence about positive association between statins and vascular calcification. They enlighten to a certain extent the possible mechanisms through which statins may enhance calcium accumulation in arterial wall, namely, by inhibition of vitamin K dependent proteins and functions involved in vascular protection.
Silvia Gancheva and Maria Zhelyazkova-Savova
Springer Science and Business Media LLC
Silvia Gancheva, Martina Kitanova, Peter Ghenev, and Maria Zhelyazkova-Savova
Pensoft Publishers
Introduction: Vitamin K (VK) is a co-factor in the post-translational gamma glutamic carboxylation of Gla-proteins. VK-dependent coagulation factors are carboxylated in the liver by VK1. Osteocalcin and Matrix-Gla protein (MGP) are carboxylated in extrahepatic tissues by VK2. A model of VK deficiency would be suitable for studying extrahepatic Gla-proteins provided that severe bleeding is prevented. Aim: The aim of this work was to adapt an established protocol of vascular calcification by warfarin-induced inactivation of MGP as a calcification inhibitor, in an attempt to create a broader state of subclinical VK deficiency and to verify its safety. Materials and methods: Two consecutive experiments, each lasting 4 weeks, were required to modify the dosing schedule of warfa­rin and VK1 and to adapt it to the Wistar rats used. The original high doses of warfarin used initially had to be halved and the protective dose of VK1 to be doubled, in order to avoid treatment-induced hemorrhagic deaths. The second experiment aimed to confirm the efficacy and safety of the modified doses. To verify the VK deficiency, blood vessels were examined histologically for calcium deposits and serum osteocalcin levels were mea­sured. Results: The original dosing schedule induced VK deficiency, manifested by arterial calcifications and dramatic changes in carboxyl­ated and uncarboxylated osteocalcin. The modified dosing regimen caused similar vascular calcification and no bleeding. Conclusion: The modified protocol of carefully balanced warfarin and VK1 doses is an effective and safe way to induce subclinical VK deficiency that can be implemented to investigate VK-dependent proteins like osteocalcin.
Silvia Gancheva, Bistra Galunska, and Maria Zhelyazkova-Savova
Wiley
Epidemiological studies reveal associations between obesity/metabolic syndrome and mood disorders. We assessed behavioural changes in rats fed diets enriched in fat and fructose in different proportions and correlated the observed alterations with biochemical changes induced by the diets. Three groups of rats were used as follows: control (C) animals fed regular rat chow, rats fed high‐fat diet (HF) and rats fed high‐fat and high‐fructose diet (HFHF). HF and HFHF animals were also given a 10% fructose solution as drinking water. Behavioural and biochemical parameters were determined. Anxiety was measured by the open‐field and the social interaction test. Depression‐like behaviour was evaluated by the forced swimming test. The object recognition test was utilized to assess effects on memory. Diet‐exposed animals displayed signs of anxiety in the open‐field (HF rats had reduced central time; HFHF rats had reduced number of central entries) and in the social interaction test (decreased time of interaction in HF group). In the forced swimming test, the immobility time was prolonged in the HFHF group. While different measures of anxiety scores correlated with visceral adiposity and dyslipidemia, results from both social interaction and forced swimming tests were significantly associated with lipid peroxidation, which in turn also correlated with the metabolic parameters. The experimental diets did not affect the object recognition memory. Both experimental diets induced metabolic derangements in rats and provoked similar anxiety‐ and depression‐like behaviours. Lipid peroxidation seems to play a role in translating diet‐induced metabolic alterations into behavioural disorders.
Silvia M. Gancheva and Maria D. Zhelyazkova-Savova
Walter de Gruyter GmbH
AbstractBackground:The metabolic syndrome is a socially important disorder of energy utilization and storage, recognized as a factor predisposing to the development of depression, anxiety and cognitive impairment in humans.Aim:In the present study we examined the effects of vitamin K2 on the behavior of rats with metabolic syndrome and looked for relationships with the effects on blood sugar.Materials and methods:Male Wistar rats were divided in four groups: a control group on a regular rat chow, a metabolic syndrome (MS) group fed a high-fat high-fructose diet, a control group treated with vitamin K2 and a MS group treated with vitamin K2. Vitamin K2 was given by gavage. At the end of the study (after 10 weeks) behavioral tests were performed and fasting blood glucose was measured. Anxiety was determined using the social interaction test and depression was assessed by the Porsolt test. Memory effects were estimated by the object recognition test. Correlations between fasting blood glucose and behavioral performance were analyzed.Results:The rats from the MS group had elevated blood glucose. They had anxiety, depression and memory deficit. Vitamin K2 normalized blood glucose, reduced anxiety and depression, but did not improve memory. Time of social interaction (inverse index of anxiety) and memory recognition were negatively correlated with blood glucose in the untreated rats but the immobility time (measure of depression) was not. When vitamin K2-treated rats were added, the correlation of blood glucose with the time of social interaction was kept, but the one with the recognition memory was lost. It might be that the anxiolytic effect of vitamin K2 in this setting is at least partly due to its effects on blood glucose, while the anti-depressant effect is glucose-independent.Conclusion:The present study demonstrated that vitamin K2 prevented the development of anxiety and depression, but did not improve the memory deficit caused by the dietary manipulation in an experimental model of metabolic syndrome. It might be that the anxiolytic effect of vitamin K2 is at least partly due to its effects on blood glucose, while the antidepressant effect is glucose-independent.
Maria Zhelyazkova-Savova, Silvia Gancheva, and Vera Sirakova
Springer Science and Business Media LLC
Valcheva-Kuzmanova, S., Zhelyazkova-Savova and M.
Portico
The main biologically active constituents of Aronia melanocarpa fruit juice (AMFJ) are polyphenolics, amongst them flavonoids, mainly anthocyanins. The aim of the present study was to investigate the effects of AMFJ (5 and 10 mL/kg) on anxiety using the social interaction test, on locomotor activity in the open field test and on working memory in the object recognition test in rats. AMFJ showed an anxiolytic-like effect which was demonstrated by a dose-dependent increase in the time of active social contacts between the test partners. The effects of both AMFJ doses were comparable to the effect of diazepam (1 mg/kg). AMFJ neither changed significantly horizontal and vertical locomotor activity, nor did it adversely affect working memory.
Maria D Zhelyazkova-Savova and Delcho K Zhelyazkov
Oxford University Press (OUP)
Abstract Isoteoline is a compound of aporphine structure derived from the alkaloid glaucine. Previous studies with isoteoline have shown antagonistic activity at 5-HT2C serotonergic receptors. We have investigated whether isoteoline interacts with 5-HT1B receptors. An isolation-induced social behavioural deficit test in mice was used as a model of stimulation of these receptors. The deficit in the behaviour of isolated mice in this experimental procedure was reported to be sensitive to 5-HT1B-receptor stimulation, since agonists at these receptors are capable of reversing it. In our study, we used N-(3-trifluoromethylphenyl) piperazine (TFMPP) (2 mg kg−1) as a reference agonist at these receptor sites. TFMPP completely restored the normal behaviour of the isolated mice. Its effect was prevented by propranolol (4 mg kg−1), a β-adrenergic receptor antagonist with a high affinity for 5-HT1B receptors, which was inactive by itself. When isoteoline was given before TFMPP, it did not prevent the effect of the latter. Given alone at doses of 0.25, 1, 4 or 8 mg kg−1, isoteoline showed an effect of its own to normalize the behaviour of isolated mice. The effect of isoteoline (1 mg kg−1, i.p.) was antagonized by pretreatment with propranolol, indicating that it was mediated through stimulation of 5-HT1B receptors. Repeated treatment with isoteoline (1 mg kg−1, 2 × 3 days, i.p.) produced tolerance to its effect and significantly attenuated the effect of TFMPP, when animals were tested 16 h after the last injection. In conclusion, the results provided functional evidence of agonist-like activity of isoteoline at the 5-HT1B receptors.
MARIA D. ZHELYAZKOVA-SAVOVA, and NEGRIN NEGREV
Elsevier BV
Serotonin, in addition to dopamine and other factors, is known to participate in the control of prolactin (PRL) and gonadotropins secretion. Isoteoline (IST), a putative serotonin antagonist and dopamine agonist, was studied for its neuroendocrine effects on PRL, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). IST was given intraperitoneally to adult male rats at doses of 0.25, 1 and 4 mg kg(-1)alone and 30 min prior to the injection of three 5-HT agonists with preferential affinity for various receptor subtypes: meta -chlorophenylpiperazine (m CPP) for 5-HT2C; 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) for 5-HT2A and 8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT) for 5-HT1A. m CPP (2.5 mg kg(-1)), DOI (2.5 mg kg(-1)) and 8-OH-DPAT (1 mg kg(-1)) increased the serum PRL levels to a similar value, without affecting FSH and LH concentrations. IST by itself modified neither PRL nor gonadotropins serum levels. IST antagonized the m CPP-induced elevation in serum PRL, the lowest dose being the most effective. It had no effect on DOI and 8-OH-DPAT-induced increases of PRL levels and produced no significant changes in the gonadotropins levels when used as an antagonist. The results are discussed in terms of the likely involvement of serotonin vs dopamine mechanism in the effect of IST. It is concluded that the inhibition of the m CPP-induced rise of PRL levels by IST confirmed the serotonin antagonistic activity, previously demonstrated for this compound in other studies. The present results are also suggestive of possible selectivity of this antagonism of IST for the 5-HT2C vs 5-HT2A and 5-HT1A receptors, all of which are involved in the control of PRL secretion.
MARIA ZHELYAZKOVA-SAVOVA, MARIA GRAZIA GIOVANNINI, and GIANCARLO PEPEU
Elsevier BV
The release of acetylcholine (ACh) from the hippocampus of freely moving rats was studied after the systemic and local administration of the 5-HT agonist chlorophenylpiperazine (mCPP), utilising the in vivo microdialysis coupled to HPLC. Intraperitoneally (i.p.) given mCPP at a dose of 8 mg kg(-1)increased the release of ACh from the hippocampus by approximately 96%. This effect was not observed when the agonist was delivered locally through the dialysis tube (reverse dialysis). The mCPP-induced increase of ACh release was prevented by i.p. mesulergine, a 5-HT2A/2C receptor antagonist, at a dose of 2 mg kg(-1). A similar effect was found with the i.p. administration of isoteoline-a putative serotonergic antagonist. Both mesulergine and isoteoline have been shown to prevent also the mCPP-induced increase of ACh release from rat cortex. In the cortex experiments both antagonists were inactive by themselves. In the hippocampus, however, isoteoline, unlike mesulergine, increased significantly the output of ACh when used alone. This effect was haloperidol-sensitive, which implies a possible dopaminergic mechanism. The results of the present work suggest that (i) the effect of mCPP on ACh release could be attributed to stimulation of 5-HT2C receptors located outside the hippocampus and (ii) isoteoline antagonizes this mCPP-induced effect irrespective of its own enhancing action on ACh release.
Maria Zhelyazkova-Savova, Maria Grazia Giovannini, and Giancarlo Pepeu
Elsevier BV