TY - JOUR AU - Szőke, Kitti AU - Kajtár, Richárd AU - Gyöngyösi, Alexandra AU - Czompa, Attila AU - Fésüs, Adina AU - Lőrincz, Eszter Boglárka AU - Petróczi, Ferenc Dániel AU - Herczegh, Pál AU - Bak, István AU - Borbás, Anikó AU - Bakai-Bereczki, Ilona AU - Lekli, István TI - Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 12 PY - 2023 IS - 9 PG - 15 SN - 2076-3921 DO - 10.3390/antiox12091714 UR - https://m2.mtmt.hu/api/publication/34125145 ID - 34125145 LA - English DB - MTMT ER - TY - JOUR AU - Csépányi, Evelin AU - Gyöngyösi, Alexandra AU - Lekli, István AU - Tósaki, Árpád AU - Bak, István TI - Beta-Carotene Affects the Effects of Heme Oxygenase-1 in Isolated, Ischemic/Reperfused Rat Hearts: Potential Role of the Iron JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 9 PG - 12 SN - 1420-3049 DO - 10.3390/molecules27093039 UR - https://m2.mtmt.hu/api/publication/32814186 ID - 32814186 N1 - Export Date: 7 September 2022 LA - English DB - MTMT ER - TY - JOUR AU - Haimhoffer, Ádám AU - Fenyvesi, Ferenc AU - Lekli, István AU - Béresová, Monika AU - Bak, István AU - Czagány, Máté AU - Vasvári, Gábor AU - Bácskay, Ildikó AU - Tóth, Judit AU - Budai, István TI - Preparation of Acyclovir-Containing Solid Foam by Ultrasonic Batch Technology JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 13 PY - 2021 IS - 10 PG - 15 SN - 1999-4923 DO - 10.3390/pharmaceutics13101571 UR - https://m2.mtmt.hu/api/publication/32246883 ID - 32246883 N1 - 322037 LA - English DB - MTMT ER - TY - JOUR AU - Gyöngyösi, Alexandra AU - Vivien, Verner AU - Bakai-Bereczki, Ilona AU - Kiss, Attila AU - Rita, Zilinyi AU - Tósaki, Árpád AU - Bak, István AU - Borbás, Anikó AU - Herczegh, Pál AU - Lekli, István TI - Basic Pharmacological Characterization of EV-34, a New H2S-Releasing Ibuprofen Derivative. JF - MOLECULES J2 - MOLECULES VL - 26 PY - 2021 IS - 3 PG - 12 SN - 1420-3049 DO - 10.3390/molecules26030599 UR - https://m2.mtmt.hu/api/publication/31841366 ID - 31841366 N1 - Export Date: 13 September 2021 AB - Cardioprotective effects of H2S are being suggested by numerous studies. Furthermore, H2S plays a role in relaxation of vascular smooth muscle, protects against oxidative stress, and modulates inflammation. Long-term high-dose use of NSAIDs, such as ibuprofen, have been associated with enhanced cardiovascular risk. The goal of the present work is the synthesis and basic pharmacological characterization of a newly designed H2S-releasing ibuprofen derivative.Following the synthesis of EV-34, a new H2S-releasing derivative of ibuprofen, oxidative stability assays were performed (Fenton and porphyrin assays). Furthermore, stability of the molecule was studied in rat serum and liver lysates. H2S-releasing ability of the EC-34 was studied with a hydrogen sulfide sensor. MTT (3-(4,5-dimethylthiazol 2-yl)-2,5-(diphenyltetrazolium bromide)) assay was carried out to monitor the possible cytotoxic effect of the compound. Cyclooxygenase (COX) inhibitory property of EV-34 was also evaluated. Carrageenan assay was carried out to compare the anti-inflammatory effect of EV-34 to ibuprofen in rat paws.The results revealed that the molecule is stable under oxidative condition of Fenton reaction. However, EV-34 undergoes biodegradation in rat serum and liver lysates. In cell culture medium H2S is being released from EV-34. No cytotoxic effect was observed at concentrations of 10, 100, 500 µM. The COX-1 and COX-2 inhibitory effects of the molecule are comparable to those of ibuprofen. Furthermore, based on the carrageenan assay, EV-34 exhibits the same anti-inflammatory effect to that of equimolar amount of ibuprofen (100 mg/bwkg).The results indicate that EV-34 is a safe H2S releasing ibuprofen derivative bearing anti-inflammatory properties. LA - English DB - MTMT ER - TY - JOUR AU - Szabados-Fürjesi, Péter AU - Pajtás, Dávid AU - Barta, Aliz AU - Csépányi, Evelin AU - Kiss, Attila AU - Tósaki, Árpád AU - Bak, István TI - Synthesis, in Vitro Biological Evaluation, and Oxidative Transformation of New Flavonol Derivatives. The Possible Role of the Phenyl-N,N-Dimethylamino Group. TS - The Possible Role of the Phenyl-N,N-Dimethylamino Group. JF - MOLECULES J2 - MOLECULES VL - 23 PY - 2018 IS - 12 PG - 15 SN - 1420-3049 DO - 10.3390/molecules23123161 UR - https://m2.mtmt.hu/api/publication/30345384 ID - 30345384 AB - Six new flavonols (6a⁻f) were synthesized with Claisen⁻Schmidt and Suzuki reactions and they were fully characterized by spectroscopic methods. In order to evaluate their antioxidant activities, their oxygen radical absorption capacity and ferric reducing antioxidant power were measured, along with their free radical scavenging activity against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and 2,2-diphenyl-1-picrylhydrazylradicals. In addition, their cytotoxicity on H9c2 cardiomyoblast cells was also assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Compounds bearing the phenyl-N,N-dimethylamino group (6a, 6c, and 6e) exhibited promising antioxidant potency and did not have any cytotoxic effect. After a consideration of these data, the oxidative transformation of the 6c compound was investigated in vitro with a chemical Fenton reaction and the identification of the formed oxidation products was performed by mass spectrometry. Two potential metabolites were detected. Based on these results, compound 6c can be a model compound for future developments. Overall, this work has proved the involvement of the phenyl-N,N-dimethylamino group in the antioxidant activity of flavonols. LA - English DB - MTMT ER - TY - JOUR AU - Czompa, Attila AU - Szőke, Kitti AU - Prokisch, Jozsef AU - Gyöngyösi, Alexandra AU - Bak, István AU - Balla, György AU - Tósaki, Árpád AU - Lekli, István TI - Aged (Black) versus Raw Garlic against Ischemia/Reperfusion-Induced Cardiac Complications JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 19 PY - 2018 IS - 4 PG - 14 SN - 1661-6596 DO - 10.3390/ijms19041017 UR - https://m2.mtmt.hu/api/publication/3365765 ID - 3365765 LA - English DB - MTMT ER - TY - JOUR AU - Csépányi, Evelin AU - Czompa, Attila AU - Szabados-Fürjesi, Péter AU - Lekli, István AU - Balla, József AU - Balla, György AU - Tósaki, Árpád AU - Bak, István TI - The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: The Role of HO-1 JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 19 PY - 2018 IS - 4 PG - 13 SN - 1661-6596 DO - 10.3390/ijms19041132 UR - https://m2.mtmt.hu/api/publication/3360047 ID - 3360047 LA - English DB - MTMT ER - TY - JOUR AU - Czompa, Attila AU - Gyöngyösi, Alexandra AU - Szőke, Kitti AU - Bak, István AU - Csépányi, Evelin AU - Haines, DD AU - Tósaki, Árpád AU - Lekli, István TI - Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium. JF - MOLECULES J2 - MOLECULES VL - 22 PY - 2017 IS - 3 SN - 1420-3049 DO - 10.3390/molecules22030488 UR - https://m2.mtmt.hu/api/publication/3212037 ID - 3212037 AB - Objective: A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods: Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin-water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results: Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO and ZO BM-treated, versus Lean rats of total cholesterol (high density lipoprotein HDL-c + low density lipoprotein LDL-c), with an inferred increase in HDL-c/LDL-c ratio-an outcome associated with decreased risk of atherosclerotic disease. Conclusions: BM extract failed to positively affect T2DM- and cardiovascular-related outcomes at a level suggesting use as a standalone treatment. Nevertheless, the encouraging effects of BM in enhancement of cardiac function, suppression of post-ischemic/reperfused infarct size extent and capacity to modulate serum cholesterol, will likely make it useful as an adjuvant therapy for the management of T2DM and related cardiovascular diseases. LA - English DB - MTMT ER - TY - JOUR AU - Csépányi, Evelin AU - Szabados-Fürjesi, Péter AU - Kiss, Attila AU - Frensemeier, LM AU - Karst, U AU - Lekli, István AU - Haines, DD AU - Tósaki, Árpád AU - Bak, István TI - Antioxidant Properties and Oxidative Transformation of Different Chromone Derivatives. JF - MOLECULES J2 - MOLECULES VL - 22 PY - 2017 IS - 4 PG - 12 SN - 1420-3049 DO - 10.3390/molecules22040588 UR - https://m2.mtmt.hu/api/publication/3212029 ID - 3212029 N1 - Megjegyzés-26639594 N1 Funding details: ESF, European Social Fund N1 Funding text: This study was supported by grants from GINOP-2.3.2-15-2016-00043, the Grant of UD, OTKA K-104017, OTKA-PD-111794 and BAROSS REG-EA-09-1-2009-0028 (LCMS-TAN). E. Csepanyi, I. Lekli and A. Tosaki assisted in fundamental research in the frame of TÁMOP-4.2.4. A/2-11-1-2012-0001 National Excellence Program-elaborating and operating an inland student and researcher personal support system was realized with personal support. The project was subsidized by the European Union and co-financed by the European Social Fund. Megjegyzés-26640244 N1 Funding details: ESF, European Social Fund N1 Funding text: This study was supported by grants from GINOP-2.3.2-15-2016-00043, the Grant of UD, OTKA K-104017, OTKA-PD-111794 and BAROSS REG-EA-09-1-2009-0028 (LCMS-TAN). E. Csepanyi, I. Lekli and A. Tosaki assisted in fundamental research in the frame of TÁMOP-4.2.4. A/2-11-1-2012-0001 National Excellence Program-elaborating and operating an inland student and researcher personal support system was realized with personal support. The project was subsidized by the European Union and co-financed by the European Social Fund. AB - Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study was the investigation of the antioxidant activity, cytotoxicity and oxidative transformation of nine chromone derivatives. First, we investigated the radical scavenging activity (ABTS), the oxygen radical absorption capacity (ORAC) and the ferric reducing antioxidant power (FRAP) of the investigated molecules. The cytotoxic effects of the compounds were tested on H9c2 cell cultures by the MTT assay. Each compound showed a significant ORAC value compared to the reference. However, the compound 865 possess significantly higher FRAP and ABTS activity in comparison with the reference and other tested molecules, respectively. Based on these assays, the compound 865 was selected for further analysis. In these experiments, we investigated the oxidative metabolism of the compound in vitro. The molecule was oxidized by the Fenton reaction, artificial porphyrin and electrochemistry; then, the formed products were identified by mass spectrometry. Four possible metabolites were detected. The results revealed the compound 865 to possess good antioxidant properties and to be stable metabolically; hence, it is worth investigating its effects in vivo. LA - English DB - MTMT ER - TY - JOUR AU - Csépányi, Evelin AU - Czompa, Attila AU - Haines, David AU - Lekli, István AU - Bakondi, Edina AU - Balla, György AU - Tósaki, Árpád AU - Bak, István TI - Cardiovascular effects of low versus high-dose beta-carotene in a rat model JF - PHARMACOLOGICAL RESEARCH J2 - PHARMACOL RES VL - 100 PY - 2015 SP - 148 EP - 156 PG - 9 SN - 1043-6618 DO - 10.1016/j.phrs.2015.07.021 UR - https://m2.mtmt.hu/api/publication/2935306 ID - 2935306 N1 - Megjegyzés-25488977 N1 Funding Details: K-104017, OTKA, Országos Tudományos Kutatási Alapprogramok Megjegyzés-25981882 N1 Funding Details: K-104017, OTKA, Országos Tudományos Kutatási Alapprogramok AB - beta-carotene (BC), a lipid-soluble tetraterpene precursor to vitamin A, widely distributed in plants, including many used in human diet, has well-known health-enhancing properties, including reducing risk of and treatment for certain diseases. Nevertheless, BC may also act to promote disease through the activity of BC derivatives that form in the presence of external toxicants such as cigarette smoke and endogenously-produced reactive oxygen species. The present investigation evaluates the dose-dependent cardioprotective and possibly harmful properties of BC in a rat model. Adult male rats were gavage-fed BC for 4 weeks, at dosages of either 0, 30 or 150mg/kg/day. Then, hearts excised from the animals were mounted in a "working heart" apparatus and subjected to 30min of global ischemia, followed by 120min of reperfusion. A panel of cardiac functional evaluations was conducted on each heart. Infarct size and total antioxidant capacity of the myocardium were assessed. Heart tissue content of heme oxygenase-1 (HO-1) by Western blot analysis; and potential direct cytotoxic effects of BC by MTT assay were evaluated. Hearts taken from rats receiving 30mg/kg/day BC exhibited significantly improved heart function at lower reperfusion times, but lost this protection at higher BC dosage and longer reperfusion times. Myocardial HO-1 content was significantly elevated dose-responsively to both BC dosage. Finally, in vitro evaluation of BC on H9c2 cells showed that the agent significantly improved vitality of these cells in a dose range of 2.5-10muM. Although data presented here do not allow for a comprehensive mechanistic explanation for reduced cardioprotection at high dose BC, it is speculated that since Fe2+ produced as a metabolite of HO-1 activity, may determine whether BC acts as an antioxidant or prooxidant agent, the strong induction of this enzyme in response to ischemia/reperfusion-induced oxidative stress may account for the high-dose BC loss of cardioprotection. LA - English DB - MTMT ER -