HEAD OF DEPARTMENT
ABOUT THE DEPARTMENT
The Department of Pharmacology of Inflammation (DPI) is focused to study the pharmacological intervention of rheumatoid arthritis (RA) in experimental conditions. The method already used in the DPI is the adjuvant-induced arthritis model (AA). This fundamental model will be complementary to collagen-induced arthritis and experimental colitis to prove the anti-inflammatory activity of the compounds studied in a broad spectrum of inflammatory animal models. Further also pharmacokinetic modelling will be applied to complete the pharmacodynamic characterisation of new molecules studied in inflammatory models (correlation by means of HPLC and/or GC-MS-MS between the plasma/tissue molecules’ concentration levels and their primary anti-inflammatory effect). Moreover, for enhancement of the anti-inflammatory effect, we will evaluate also new advanced drug delivery systems such as micro- and nano-emulsions, niosomes and liposomes. The application of implantable bionic hydrogel enriched with selected natural compounds for repairing articular cartilage lesions will be also studied. These procedures should increase the bioavailability of compounds studied. This altogether will create a platform for performing clinical studies with new substances.
The objectives of the research at the DPI might be divided into three arms. The first arm is the pathophysiological study of inflammatory autoimmune processes. Our future perspectives will be in research focused on better understanding and treatment of different pathological conditions accompanying RA such as cachexia, cardiovascular complications and depression connected with neuro-inflammation. A comprehensive interdisciplinary approach will be utilized to evaluate the efficacy and mode of action of C43, a new synthetic aryl hydrocarbon receptor (AhR) ligand that has already exerted promising Treg-stimulatory effects. Pre-clinical evaluation of the C43 effect in an animal model of RA will include in vivo bioimaging and pharmacokinetic profile, which will establish the dose range to be used in AA. Cellular and molecular targets of C43 will be identified.
The relationship between pathological findings and their treatment has not been well established at many levels. Thus, the pharmacological research of selected natural and synthetic molecules will be launched as the second arm of our objectives.
The third arm will be focused on the elucidation of the mechanism of action of the compounds studied.
Standard treatment of RA with methotrexate (MTX) and glucocorticoids (GC) may worsen cachexia. Thus, an important strategy of our research will be the suppression of cachexia using combination therapy, which will be based on the addition of natural anti-inflammatory substances to MTX and GC. In experimental arthritis, we will also investigate the effect of drugs and natural substances on markers of catabolism and anabolism of skeletal muscle, and on markers of systemic inflammation and oxidative stress in plasma, which will help us to elucidate the mechanisms of inflammatory cachexia and it’s affecting by monotherapy and combination therapy.
Our results from last year show that combinations of natural substances and methotrexate (MTX) reduced inflammation more effectively than MTX alone. Combination therapy of MTX with natural substances that have the potential to improve efficacy and reduce side effects of MTX is one possible direction in the adjuvant treatment of RA. On other hand, each new combination needs to be carefully tested in animal models before administering to RA patients to avoid negative effects which could occur in some specific cases.
For the materialisation of our strategy, we will cooperate with our scientific partners at the national (Comenius University: Medical and Pharmaceutical Faculty, Slovak Technical University) as well as at the international level (Pharmaceutical Faculty of the University of Lisbon, Vietnam Academy of Science and Technology, the Dalian University of Technology in China, 1st Medical faculty of Charles University in Prague, the University of Ioannina in Greece and Institute for Biological Research “Siniša Stanković”- National Institute of the Republic of Serbia). For the realisation of clinical studies also the State Institute for Drug Control will be addressed.
Inflammation, rheumatoid arthritis, adjuvant arthritis, cachexia, oxidative stress, natural compounds, combination therapy
ELISA, Western blot, RT-PCR, spectrophotometry
BAUEROVÁ, Katarína** – KUCHARSKÁ, Jarmila – PONIŠT, Silvester – SLOVÁK, Lukáš – ŠVÍK, Karol – JAKUŠ, Vladimír – MUCHOVÁ, Jana. The Role of Endogenous Antioxidants in the Treatment of Experimental Arthritis. In Antioxidants. – London : IntechOpen, 2019, chapter 8, p. 1-23. ISBN 978-1-78923-920-1.
PONIŠT, Silvester – DRÁFI, František – KUNCÍROVÁ, Viera – MIHALOVÁ, Danica – RAČKOVÁ, Lucia – DANIŠOVIČ, Ľuboš – ONDREJIČKOVÁ, Oľga – TUMOVÁ, Ingrid – TRUNOVÁ, Oľga – FEDOROVA, Tatiana – BAUEROVÁ, Katarína. Effect of carnosine in experimental arthritis and on primary culture chondrocytes. In Oxidative medicine and cellular longevity, 2016, vol. 2016, article ID 8470589, 11 p.
SÝKORA, T.** – BABÁL, Pavel – KURACINOVÁ, Kristína – DRÁFI, František – PONIŠT, Silvester – DVORÁKOVÁ, M. – JANEGA, Pavol – BAUEROVÁ, Katarína. Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis. In International Journal of Molecular Sciences, 2021, vol. 22, Iss. 16, art. no. 8662.
TSIKLAURI, Lia – ŠVÍK, Karol – CHRASTINA, Martin – PONIŠT, Silvester – DRÁFI, František – SLOVÁK, Lukáš – ALANIA, Mery – KEMERTELIDZE, Ether – BAUEROVÁ, Katarína**. Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis. In Nutrients, 2021, vol. 13, no. 4, art. no. 1268.
KUCHARSKÁ, Jarmila – PONIŠT, Silvester – VANČOVÁ, Olga – GVOZDJÁKOVÁ, Anna – ULIČNÁ, Oľga – SLOVÁK, Lukáš – TAGHDISIESFEJÍR, Mohsen – BAUEROVÁ, Katarína**. Treatment With Coenzyme Q10, ω-3-Polyunsaturated Fatty Acids and Their Combination Improved Bioenergetics and Levels of Coenzyme Q9 and Q10 in Skeletal Muscle Mitochondria in Experimental Model of Arthritis – Treatment With Coenzyme Q(10), omega-3-Polyunsaturated Fatty Acids and Their Combination Improved Bioenergetics and Levels of Coenzyme Q(9) and Q(10) in Skeletal Muscle Mitochondria in Experimental Model of Arthritis. In Physiological Research, 2021, vol. 70, no. 5, p. 723-733.