TY - JOUR AU - Tánczos, Bence AU - Vass, Virág AU - Szabó, Erzsébet AU - Lovas, Miklós AU - Kattoub, Rasha Ghanem AU - Bakai-Bereczki, Ilona AU - Borbás, Anikó AU - Herczegh, Pál AU - Tósaki, Árpád TI - Effects of H2S-donor ascorbic acid derivative and ischemia/reperfusion-induced injury in isolated rat hearts JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 195 PY - 2024 IS - - SP - 106721 SN - 0928-0987 DO - 10.1016/j.ejps.2024.106721 UR - https://m2.mtmt.hu/api/publication/34572686 ID - 34572686 LA - English DB - MTMT ER - TY - JOUR AU - Herczeg, Mihály AU - Demeter, Fruzsina AU - Nagy, Tibor AU - Rusznyák, Ágnes AU - Hodek, Jan AU - Sipos, Éva AU - Lekli, István AU - Fenyvesi, Ferenc AU - Weber, Jan AU - Kéki, Sándor AU - Borbás, Anikó TI - Block Synthesis and Step-Growth Polymerization of C-6-Sulfonatomethyl-Containing Sulfated Malto-Oligosaccharides and Their Biological Profiling JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 1 SN - 1661-6596 DO - 10.3390/ijms25010677 UR - https://m2.mtmt.hu/api/publication/34502650 ID - 34502650 AB - Highly sulfated malto-oligomers, similar to heparin and heparan-sulfate, have good antiviral, antimetastatic, anti-inflammatory and cell growth inhibitory effects. Due to their broad biological activities and simple structure, sulfated malto-oligomer derivatives have a great therapeutic potential, therefore, the development of efficient synthesis methods for their production is of utmost importance. In this work, preparation of α-(1→4)-linked oligoglucosides containing a sulfonatomethyl moiety at position C-6 of each glucose unit was studied by different approaches. Malto-oligomeric sulfonic acid derivatives up to dodecasaccharides were prepared by polymerization using different protecting groups, and the composition of the product mixtures was analyzed by MALDI-MS methods and size-exclusion chromatography. Synthesis of lower oligomers was also accomplished by stepwise and block synthetic methods, and then the oligosaccharide products were persulfated. The antiviral, anti-inflammatory and cell growth inhibitory activity of the fully sulfated malto-oligosaccharide sulfonic acids were determined by in vitro tests. Four tested di- and trisaccharide sulfonic acids effectively inhibited the activation of the TNF-α-mediated inflammatory pathway without showing cytotoxicity. LA - English DB - MTMT ER - TY - JOUR AU - Klusóczki, Ágnes AU - Oláh, Boglárka AU - Hosszú, Dominik AU - Fenyvesi, Ferenc AU - Gálné Remenyik, Judit AU - Homoki, Judit Rita AU - Gyöngyösi, Alexandra AU - Bácskay, Ildikó AU - Váradi, Judit TI - Effectiveness of Anthocyanin-Rich Sour Cherry Extract on Gliadin-Induced Caco-2 Barrier Damage JF - NUTRIENTS J2 - NUTRIENTS VL - 15 PY - 2023 IS - 18 SN - 2072-6643 DO - 10.3390/nu15184022 UR - https://m2.mtmt.hu/api/publication/34160368 ID - 34160368 AB - Several types of gluten-related disorders are known, in which the common starting point is gluten-induced zonulin release. Zonulin results in varying degrees of increased permeability in certain gluten-related disorders but is largely responsible for the development of further pathogenic processes and symptoms. Therefore, it is important to know the barrier-modulating role of individual nutritional components and to what extent the antioxidant substance supports the protection of gliadin-induced membrane damage with its radical scavenging capacity. We investigated the pH dependence of the gliadin-anthocyanin interaction using UV photometry, during which a concentration-dependent interaction was observed at pH 6.8. The barrier modulatory effect of the anthocyanin-rich sour cherry extract (AC) was analyzed on Caco-2 cell culture with pepsin-trypsin-resistant gliadin (PT-gliadin) exposure by TEER measurement, zonula occludens-1 (ZO-1), and Occludin immunohistochemistry. In addition to the TEER-reducing and TJ-rearranging effects of PT-gliadin, NF-κB activation, an increase in cytokine (TNF-α, IFN-γ, and IL-8) release, and mitochondrial ROS levels were observed. We confirmed the anti-inflammatory, stabilizing, and restoring roles of AC extract during gliadin treatment on the Caco-2 monolayer. The extract was able to significantly reduce cytokine and ROS levels despite the known interaction of the main components of the extract with PT-gliadin. LA - English DB - MTMT ER - 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 - Frei, Gréta AU - Haimhoffer, Ádám AU - Csapó, Enikő AU - Bodnár, Krisztina AU - Vasvári, Gábor AU - Nemes, Dániel AU - Lekli, István AU - Gyöngyösi, Alexandra AU - Bácskay, Ildikó AU - Siposné Fehér, Pálma AU - Józsa, Liza TI - In Vitro and In Vivo Efficacy of Topical Dosage Forms Containing Self-Nanoemulsifying Drug Delivery System Loaded with Curcumin JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 8 SP - 2054 SN - 1999-4923 DO - 10.3390/pharmaceutics15082054 UR - https://m2.mtmt.hu/api/publication/34124819 ID - 34124819 AB - The external use of curcumin is rare, although it can be a valuable active ingredient in the treatment of certain inflammatory diseases. The aim of our experimental work was to formulate topical dosage forms containing curcumin for the treatment of atopic dermatitis. Curcumin has extremely poor solubility and bioavailability, so we have tried to increase it with the usage of self-emulsifying drug delivery systems. Creams and gels were formulated using penetration-enhancing surfactants and gelling agents. The release of the drug from the vehicle and its penetration through the membrane were determined using a Franz diffusion cell. An MTT cytotoxicity and in vitro antioxidant assays were performed on HaCaT cell line. The in vivo anti-inflammatory effect of the preparations was tested by measuring rat paw edema. In addition, we examined the degree of inflammation induced by UV radiation after pretreatment with the cream and the gel on rats. For the gels containing SNEDDS, the highest penetration was measured after half an hour, while for the cream, it took one hour to reach the maximum concentration. The gel containing Pemulen TR-1 showed the highest drug release. It was determined that the curcumin-containing preparations can be safely applied on the skin and have antioxidant effects. The animal experiments have proven the effectiveness of curcumin-containing topical preparations. LA - English DB - MTMT ER - TY - JOUR AU - To Quoc, Thinh AU - Bíró, Krisztina AU - Pető, Ágota AU - Kósa, Dóra AU - Sinka, Dávid AU - Lekli, István AU - Kiss, Attila AU - Budai, István AU - Béresová, Monika AU - Vecsernyés, Miklós AU - Siposné Fehér, Pálma AU - Bácskay, Ildikó AU - Ujhelyi, Zoltán TI - Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 11 PG - 15 SN - 1420-3049 DO - 10.3390/molecules28114406 UR - https://m2.mtmt.hu/api/publication/33938541 ID - 33938541 AB - Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood–brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product. LA - English DB - MTMT ER - TY - JOUR AU - Szőke, Kitti AU - Bódi, Beáta AU - Hendrik, Zoltán AU - Czompa, Attila AU - Gyöngyösi, Alexandra AU - Haines, Donald David AU - Papp, Zoltán AU - Tósaki, Árpád AU - Lekli, István TI - Rapamycin treatment increases survival, autophagy biomarkers and expression of the anti‐aging klotho protein in elderly mice JF - PHARMACOLOGY RESEARCH AND PERSPECTIVES J2 - PHARMACOL RES PERSPECT VL - 11 PY - 2023 IS - 3 PG - 11 SN - 2052-1707 DO - 10.1002/prp2.1091 UR - https://m2.mtmt.hu/api/publication/33828248 ID - 33828248 AB - Previous investigations have demonstrated that treatment of animals with rapamycin increases levels of autophagy, which is a process by which cells degrade intracellular detritus, thus suppressing the emergence of senescent cells, whose pro-inflammatory properties, are primary drivers of age-associated physical decline. A hypothesis is tested here that rapamycin treatment of mice approaching the end of their normal lifespan exhibits increased survival, enhanced expression of autophagic proteins; and klotho protein—a biomarker of aging that affects whole organism senescence, and systemic suppression of inflammatory mediator production. Test groups of 24-month-old C57BL mice were injected intraperitoneally with either 1.5 mg/kg/week rapamycin or vehicle. All mice administered rapamycin survived the 12-week course, whereas 43% of the controls died. Relative to controls, rapamycin-treated mice experienced minor but significant weight loss; moreover, nonsignificant trends toward decreased levels of leptin, IL-6, IL-1β, TNF-α, IL-1α, and IGF-1, along with slight elevations in VEGF, MCP-1 were observed in the blood serum of rapamycin-treated mice. Rapamycin-treated mice exhibited significantly enhanced autophagy and elevated expression of klotho protein, particularly in the kidney. Rapamycin treatment also increased cardiomyocyte Ca2+-sensitivity and enhanced the rate constant of force re-development, which may also contribute to the enhanced survival rate in elderly mice. LA - English DB - MTMT ER - TY - JOUR AU - Vass, Virág AU - Szabó, Erzsébet AU - Bakai-Bereczki, Ilona AU - Debreczeni, Nóra AU - Borbás, Anikó AU - Herczegh, Pál AU - Tósaki, Árpád TI - Reperfusion-induced injury and the effects of the dithioacetate type hydrogen sulfide donor ibuprofen derivative, BM-88, in isolated rat hearts JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 185 PY - 2023 SN - 0928-0987 DO - 10.1016/j.ejps.2023.106449 UR - https://m2.mtmt.hu/api/publication/33768628 ID - 33768628 N1 - Export Date: 11 October 2023 CODEN: EPSCE LA - English DB - MTMT ER - TY - JOUR AU - Bernát, Brigitta Renáta AU - Erdelyi, Rita AU - Fazekas, László Ádám AU - Garami, Greta AU - Szekeres, Réka Mária AU - Takács, Barbara AU - Bombicz, Mariann AU - Varga, Balázs AU - Sárkány, Fruzsina AU - Ráduly, Arnold AU - Romanescu, Dana Diana AU - Papp, Zoltán AU - Tóth, Attila AU - Szilvássy, Zoltán AU - Juhász, Béla AU - Priksz, Dániel TI - Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 16 PY - 2023 IS - 3 PG - 22 SN - 1424-8247 DO - 10.3390/ph16030359 UR - https://m2.mtmt.hu/api/publication/33703433 ID - 33703433 N1 - Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Dentoalveolar Surgery, Faculty of Dentistry, University of Debrecen, Debrecen, H-4032, Hungary Department of Operative Techniques and Surgical Research, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Diabetology, Pelican Clinical Hospital, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, 410087, Romania Export Date: 5 October 2023 Correspondence Address: Priksz, D.; Department of Pharmacology and Pharmacotherapy, Hungary; email: priksz.daniel@pharm.unideb.hu Chemicals/CAS: cefuroxime, 55268-75-2, 56238-63-2; dipyrone, 50567-35-6, 5907-38-0, 68-89-3; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; o (2 hydroxy 3 piperidinopropyl)nicotinic amidoxime, 66611-37-8 Tradenames: bgp 15, Sigma Aldrich, Germany; bgp 15, Merck, Germany Manufacturers: Merck, Germany; Sigma Aldrich, Germany Funding details: ÚNKP-21-2-I-DE-392 Funding details: European Commission, EC Funding details: Debreceni Egyetem, DE, GINOP-2.3.4-15-2020-00008, TKP2020-NKA-04 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, 2020-4.1.1-TKP2020 Funding details: Innovációs és Technológiai Minisztérium Funding text 1: This research was supported by the European Union, the State of Hungary, and the University of Debrecen under grant number GINOP-2.3.4-15-2020-00008 (D.P., R.M.S., B.T., B.V., M.B., B.B., B.J., Z.S.). Project no. TKP2020-NKA-04 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the 2020-4.1.1-TKP2020 funding scheme. The research was financed by the Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary (TKP2020-NKA-04), within the framework of the Space Sciences thematic program of the University of Debrecen. The publication was supported by the ÚNKP-21-2-I-DE-392 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. (B.B., D.P.) AB - Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters. First, dose escalation studies (40–160 mg/kg BGP-15), ECG parameters, and 24 h HRV parameters were assessed. After, rats were divided into Control, Control+BGP-15, ISO, and ISO+BGP-15 subgroups for 2 weeks. ECG recordings were obtained from conscious rats, arrhythmias and HRV parameters were assessed, and echocardiography was carried out. ISO-BGP-15 interaction was also evaluated on an isolated canine cardiomyocyte model. BGP-15 had no observable effects on the ECG waveforms; however, it decreased heart rate. HRV monitoring showed that BGP-15 increased RMSSD, SD1, and HF% parameters. BGP-15 failed to counteract 1 mg/kg ISO-induced tachycardia, but diminished the ECG of ischemia and suppressed ventricular arrhythmia incidence. Under echocardiography, after low-dose ISO injection, BGP-15 administration lowered HR and atrial velocities, and increased end-diastolic volume and ventricle relaxation, but did not counteract the positive inotropic effects of ISO. Two weeks of BGP-15 treatment also improved diastolic function in ISO-treated rats. In isolated cardiomyocytes, BGP-15 prevented 100 nM ISO-induced aftercontractions. Here, we show that BGP-15 increases vagally mediated HRV, reduces arrhythmogenesis, enhances left ventricle relaxation, and suppresses the aftercontractions of cardiomyocytes. As the drug is well tolerated, it may have a clinical value in preventing fatal arrhythmias. LA - English DB - MTMT ER - TY - JOUR AU - Gyöngyösi, Alexandra AU - Csáki, Nikolett AU - Pető, Ágota AU - Szőke, Kitti AU - Fenyvesi, Ferenc AU - Bácskay, Ildikó AU - Lekli, István TI - BGP-15 Protects against Doxorubicin-Induced Cell Toxicity via Enhanced Mitochondrial Function JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 6 PG - 13 SN - 1661-6596 DO - 10.3390/ijms24065269 UR - https://m2.mtmt.hu/api/publication/33691053 ID - 33691053 AB - Doxorubicin (DOX) is an efficacious and commonly used chemotherapeutic agent. However, its clinical use is limited due to dose-dependent cardiotoxicity. Several mechanisms have been proposed to play a role in DOX-induced cardiotoxicity, such as free radical generation, oxidative stress, mitochondrial dysfunction, altered apoptosis, and autophagy dysregulation. BGP-15 has a wide range of cytoprotective effects, including mitochondrial protection, but up to now, there is no information about any of its beneficial effects on DOX-induced cardiotoxicity. In this study, we investigated whether the protective effects of BGP-15 pretreatment are predominantly via preserving mitochondrial function, reducing mitochondrial ROS production, and if it has an influence on autophagy processes. H9c2 cardiomyocytes were pretreated with 50 mu M of BGP-15 prior to different concentrations (0.1; 1; 3 mu M) of DOX exposure. We found that BGP-15 pretreatment significantly improved the cell viability after 12 and 24 h DOX exposure. BGP-15 ameliorated lactate dehydrogenase (LDH) release and cell apoptosis induced by DOX. Additionally, BGP-15 pretreatment attenuated the level of mitochondrial oxidative stress and the loss of mitochondrial membrane potential. Moreover, BGP-15 further slightly modulated the autophagic flux, which was measurably decreased by DOX treatment. Hence, our findings clearly revealed that BGP-15 might be a promising agent for alleviating the cardiotoxicity of DOX. This critical mechanism appears to be given by the protective effect of BGP-15 on mitochondria. LA - English DB - MTMT ER -