Agnieszka Góralczyk

Medical University of Lublin

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Jarogniew J. Łuszczki

Medical University of Lublin

Paula Wróblewska-Łuczka

Medical University of Lublin

Paweł Marzęda

Medical University of Lublin

Magdalena Florek-Łuszczki

Instytut Medycyny Wsi im. Witolda Chodźki

Katarzyna Załuska-Ogryzek

Medical University of Lublin

Gareth J. Sanger

Queen Mary University of London

Aneta Grabarska

Medical University of Lublin

Kesava R. Mannur

Homerton University Hospital

Anna Stachniuk

Medical University of Lublin

Umesh Parampalli

Shrewsbury and Telford Hospital NHS Trust

Cooperative Institutions

Medical University of Lublin

Instytut Medycyny Wsi im. Witolda Chodźki

Central Institute of Mental Health

Homerton University Hospital

Queen Mary University of London

University College London

GlaxoSmithKline (United Kingdom)

John Paul II Catholic University of Lublin

Maria Curie-Skłodowska University

Weatherford College

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation

International Journal of Molecular Sciences (2023)

Jarogniew J. Łuszczki Hubert Bojar Agnieszka Góralczyk Krystyna Skalicka‐Woźniak

Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model.

Phenobarbital

Borneol

10.3390/ijms24021395

Cite

Citations (5)

Antiproliferative effects of LY-2183240 combined with various chemotherapeutic drugs in an isobolographic in vitro model of malignant melanoma

European Journal of Pharmacology (2024)

Paweł Marzęda Paula Wróblewska-Łuczka Magdalena Florek-Łuszczki Agnieszka Góralczyk Jarogniew J. Łuszczki

Mitoxantrone

MTT assay

Carboplatin

10.1016/j.ejphar.2024.176937

Cite

Citations (1)

Synergy, Additivity and Antagonism between Esculetin and Six Commonly Used Chemotherapeutics in Various Malignant Melanoma Cell Lines—An Isobolographic Analysis

Molecules (2023)

Paula Wróblewska-Łuczka Agnieszka Góralczyk Jarogniew J. Łuszczki

(1) Malignant melanomas are dangerous skin cancers, and the treatment of melanomas with various cytostatic drugs often causes side effects and after their prolonged use resistance to these drugs appears. The aim of this study was to evaluate the anticancer effects of esculetin (a simple coumarin) and to assess pharmacodynamic interactions between esculetin and six commonly used cytostatic drugs (cisplatin, epirubicin, docetaxel, paclitaxel, mitoxantrone and vemurafenib) using an isobolographic analysis. (2) The experiments were carried out on four human malignant melanoma cell lines (FM55P, A375, FM55M2 and SK-MEL28). The effects of esculetin on viability, cell proliferation and cytotoxicity were verified in the range of concentrations of 2–200 μM. (3) Esculetin inhibited, in a dose-dependent manner, malignant melanoma cell viability and proliferation. The IC50 for esculetin ranged from 18.20 ± 2.93 to 120.64 ± 30.39 μM depending on the melanoma cell lines used. The combinations of esculetin with epirubicin and vemurafenib showed antagonistic interactions, the combinations of esculetin with cisplatin, docetaxel and paclitaxel showed additive interactions. For the combinations of esculetin with mitoxantrone, the isobolographic analysis displayed synergy. (4) In the treatment of malignant melanoma, esculetin should not be combined with epirubicin or vemurafenib, due to the reduction of their anticancer effects, while the synergistic interactions (esculetin + mitoxantrone) deserve a preclinical recommendation as a beneficial combination during anticancer therapy.

Epirubicin

Mitoxantrone

Viability assay

10.3390/molecules28093889

Cite

Citations (2)

AM1172 (a hydrolysis-resistant endocannabinoid analog that inhibits anandamide cellular uptake) reduces the viability of the various melanoma cells, but it exerts significant cytotoxic effects on healthy cells: an in vitro study based on isobolographic analysis

Pharmacological Reports (2023)

Paweł Marzęda Paula Wróblewska-Łuczka Magdalena Florek-Łuszczki Agnieszka Góralczyk Jarogniew J. Łuszczki

Abstract Background Despite great advances in our understanding of the impact of cannabinoids on human organism, many of their properties still remain undetermined, including their potential antineoplastic effects. This study was designed to assess the anti-proliferative and cytotoxic effects of AM1172 (a hydrolysis-resistant endocannabinoid analog that inhibits anandamide cellular uptake) administered alone and in combinations with docetaxel (DOCX), paclitaxel (PACX), mitoxantrone (MTX) and cisplatin (CDDP) on various human malignant melanoma A375, FM55P, SK-MEL 28 and FM55M2 cell lines. Materials In the MTT, LDH, and BrdU assays, the potency and safety of AM1172 when administered alone and in combinations with DOCX, PACX, MTX, and CDDP were determined. Results The isobolographic analysis revealed that combinations of AM1172 with PACX, DOCX, MTX, and CDDP exerted additive interactions, except for a combination of AM1172 with PACX in primary melanoma A375 cell line, for which synergy was observed (* p <0.05). Nevertheless, AM1172 when administered alone produced cytotoxic effects on healthy human melanocytes (HEMa-LP) and human keratinocytes (HaCaT), which unfortunately limits its potential therapeutic utility. Conclusions AM1172 cannot be used separately as a chemotherapeutic drug, but it can be combined with PACX, DOCX, MTX, and CDDP, offering additive interactions in terms of the anti-proliferative effects in various malignant melanoma cell lines.

HaCaT

10.1007/s43440-023-00557-2

Cite

Citations (2)

Drugs acting at 5‐HT₄, D₂, motilin, and ghrelin receptors differ markedly in how they affect neuromuscular functions in human isolated stomach

Neurogastroenterology & Motility (2014)

John Broad Agnieszka Góralczyk Kesava R. Mannur George E. Dukes Gareth J. Sanger

Abstract Background Progress in identifying safer, effective drugs to increase gastric emptying is impeded by failed clinical trials. One potential reason for failure is lack of translation from animal models to the human condition. To make progress, the actions of existing drugs and new therapeutic candidates need to be understood in human isolated stomach. Methods Neuromuscular activities were evoked in human gastric antrum circular muscle by electrical field stimulation ( EFS ), defined phenotypically using pharmacological tools. Key Results EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. The 5‐ HT 4 receptor agonist/D 2 antagonist metoclopramide and the selective 5‐ HT 4 agonist prucalopride, facilitated contractions in the absence (respectively, E max 95 ± 29% and 42 ± 9%, n = 3–6 each concentration) and presence (139 ± 38%, 55 ± 13%, n = 3–5) of the NO synthase inhibitor L‐ NAME , without affecting submaximal contractions to carbachol; the 5‐ HT 4 antagonist SB 204070 prevented facilitation by metoclopramide 100 μ M (respectively, −5 (range −26 to 34) and 167 (12–1327)% in presence and absence; n = 5–6). The selective motilin receptor agonist camicinal provided considerably greater facilitation (478 (12–2080)% at 30 μ M, n = 8). Domperidone (0.001–100 μ M; n = 3–6) and acylated or des‐acylated ghrelin (1–300 nM; n = 2–4) had no consistent activity, even with protease inhibitors. Conclusions & Inferences 5‐ HT 4 receptor agonists show different efficacies. Motilin receptor activation has greater potential to increase gastric emptying, whereas ghrelin and D 2 receptor antagonism have no direct activity. Drugs stimulating human gastric motility directly can act regardless of disease mechanisms, whereas drugs without direct activity but an ability to block nausea/vomiting may be effective only if these symptoms exist.

Motilin

Metoclopramide

10.1111/nmo.12338

Cite

Citations (29)

Isobolographic interactions of cannabidiol and AM 1172 with cisplatin in human neuroblastoma and glioblastoma cell lines: an in vitro study

Chemico-Biological Interactions (2025)

Katarzyna Załuska-Ogryzek Paula Wróblewska-Łuczka Agnieszka Góralczyk Jarogniew J. Łuszczki

10.1016/j.cbi.2025.111392

Cite

Citations (0)

Farnesoid X receptor ‐ a molecular predictor of weight loss after vertical sleeve gastrectomy?

Obesity Science & Practice (2019)

Fiona Scott Shezan Elahi Miriam Adebibe Umesh Parampalli Kesava R. Mannur

To determine the expression of the bile acid receptor, farnesoid X (FXR), in human gastric mucosa and investigate correlations between expression and body-mass index (BMI) and in patients with obesity, with changes in weight and BMI following vertical sleeve gastrectomy (VSG).Human gastric mucosa was obtained from normal/overweight individuals (macroscopically-normal tissue following surgery for malignancy) or from patients with obesity (VSG). The expression of FXR and its isoforms (FXRα, FXRβ) were examined by quantitative PCR and compared with the G protein-coupled bile acid receptor, GPBA. In patients with obesity, changes in BMI and weight loss were determined following VSG.FXRα was the predominant isoform in normal/overweight individuals. FXR expression was higher in patients with obesity but GPBA receptor expression was unchanged. For those with obesity (n = 19), no correlation was found between FXR expression and change in Body-Mass Index (BMI)/month or weight loss/month, taken 3 ± 1 months after surgery, or in BMI or weight at surgery.Obesity is associated with increased FXR expression in the gastric mucosa. The findings are preliminary but suggest that this increase in FXR expression is a consequence of obesity, rather than its cause.

Farnesoid X receptor

Sleeve gastrectomy

10.1002/osp4.337

Cite

Citations (4)

The effect of exenatide (a GLP-1 analogue) and sitagliptin (a DPP-4 inhibitor) on asymmetric dimethylarginine (ADMA) metabolism and selected biomarkers of cardiac fibrosis in rats with fructose-induced metabolic syndrome

Biochemical Pharmacology (2023)

Grażyna Wójcicka Anna Pradiuch Emilia Fornal Anna Stachniuk Agnieszka Korolczuk

Asymmetric dimethylarginine

Cardiac Fibrosis

Myocardial fibrosis

10.1016/j.bcp.2023.115637

Cite

Citations (4)

Fraxetin Interacts Additively with Cisplatin and Mitoxantrone, Antagonistically with Docetaxel in Various Human Melanoma Cell Lines—An Isobolographic Analysis

International Journal of Molecular Sciences (2022)

Paula Wróblewska-Łuczka Aneta Grabarska Agnieszka Góralczyk Paweł Marzęda Jarogniew J. Łuszczki

Malignant melanoma is a skin cancer characterized by rapid development, poor prognosis and high mortality. Due to the frequent drug resistance and/or early metastases in melanoma, new therapeutic methods are urgently needed. The study aimed at assessing the cytotoxic and antiproliferative effects of scoparone and fraxetin in vitro, when used alone and in combination with three cytostatics: cisplatin, mitoxantrone, and docetaxel in four human melanoma cell lines. Our experiments showed that scoparone in the concentration range tested up to 200 µM had no significant effect on the viability of human malignant melanoma (therefore, it was not possible to evaluate it in combination with other cytostatics), while fraxetin inhibited cell proliferation with IC50 doses in the range of 32.42–73.16 µM, depending on the cell line. Isobolographic analysis allowed for the assessment of the interactions between the studied compounds. Importantly, fraxetin was not cytotoxic to normal keratinocytes (HaCaT) and melanocytes (HEMa-LP), although it slightly inhibited their viability at high concentrations. The combination of fraxetin with cisplatin and mitoxantrone showed the additive interaction, which seems to be a promising direction in melanoma therapy. Unfortunately, the combination of fraxetin with docetaxel may not be beneficial due to the antagonistic antiproliferative effect of both drugs used in the mixture.

Mitoxantrone

HaCaT

Viability assay

10.3390/ijms24010212

Cite

Citations (5)

Daphnetin, a Coumarin with Anticancer Potential against Human Melanoma: In Vitro Study of Its Effective Combination with Selected Cytostatic Drugs

Cells (2023)

Paula Wróblewska-Łuczka Agnieszka Góralczyk Jarogniew J. Łuszczki

(1) The treatment of metastatic or drug-resistant melanoma is still a significant therapeutic problem. The aim of this study was to evaluate the anticancer potential of daphnetin (7,8-dihydroxycoumarin) and its combinations with five different cytostatic drugs (mitoxantrone, docetaxel, vemurafenib, epirubicin and cisplatin). (2) The viability, proliferation and cytotoxicity of daphnetin against four human malignant melanoma cell lines were evaluated. The interactions were assessed using isobolographic analysis for the combinations of daphnetin with each of the five cytostatic drugs. (3) Daphnetin showed anticancer activity against malignant melanoma, with IC50 values ranging from 40.48 ± 10.90 µM to 183.97 ± 18.82 µM, depending on the cell line. The combination of daphnetin with either vemurafenib or epirubicin showed an antagonistic interaction. Moreover, additive interactions were observed for the combinations of daphnetin with cisplatin and docetaxel. The most desirable synergistic interactions for human melanoma metastatic cell lines were observed for the combination of daphnetin with mitoxantrone. (4) The obtained results suggest that daphnetin should not be combined with vemurafenib or epirubicin in the treatment of malignant melanoma due to the abolition of their anticancer effects. The combination of daphnetin with mitoxantrone is beneficial in the treatment of metastatic melanoma due to their synergistic interaction.

Epirubicin

Mitoxantrone

Combination therapy

10.3390/cells12121593

Cite

Citations (6)