Centre of Experimental Medicine SAS
Topic
Administration of paraxanthine and 3-nitro fatty acids in monotherapy and in combinations with methotrexate in experimental arthritis.
PhD. program
Pharmacology
Year of admission
2026
Name of the supervisor
PharmDr. Silvester Poništ, PhD.
Contact:
Receiving school
Faculty of Pharmacy, Comenius University
Annotation
Administration of paraxanthine and 3-nitro fatty acids in monotherapy and in combinations with methotrexate.
Rheumatoid arthritis (RA) is characterized not only by systemic inflammation but also by distinct shifts in cellular bioenergetics, a phenomenon known as immuno-metabolic reprogramming. In this process, activated immune cells shift their metabolism from oxidative phosphorylation to glycolysis to fuel rapid proliferation. While Methotrexate (MTX) remains the gold standard in RA therapy, its use is frequently limited by toxicity and adverse effects This dissertation investigates the therapeutic potential of paraxanthine (the primary metabolite of caffeine) and 3-nitro fatty acids (NO-FAs), administered both as monotherapies and in combination with MTX in a rat model of adjuvant arthritis (AA).
The primary objective is to evaluate how these bioactive substances modulate the crosstalk between inflammation and metabolic dysfunction. The study specifically monitors the restoration of metabolic homeostasis by analyzing parameters of oxidative stress, pro-inflammatory cytokines, and lipid metabolism profiles. A focal point of the research is the role of ketone bodies. As endogenous signaling molecules with potent anti-inflammatory properties, the study assesses whether paraxanthine and NO-FAs influence ketogenesis or synergize with ketone-driven pathways to suppress joint pathology.
By correlating changes in lipid metabolism with clinical arthritis scores, this work aims to demonstrate that targeting metabolic checkpoints can enhance the efficacy of MTX. This suggests a novel pharmacological strategy to induce favorable immuno-metabolic reprogramming, potentially allowing for dose reduction of cytostatic drugs and minimizing systemic toxicity.
Rheumatoid arthritis (RA) is characterized not only by systemic inflammation but also by distinct shifts in cellular bioenergetics, a phenomenon known as immuno-metabolic reprogramming. In this process, activated immune cells shift their metabolism from oxidative phosphorylation to glycolysis to fuel rapid proliferation. While Methotrexate (MTX) remains the gold standard in RA therapy, its use is frequently limited by toxicity and adverse effects This dissertation investigates the therapeutic potential of paraxanthine (the primary metabolite of caffeine) and 3-nitro fatty acids (NO-FAs), administered both as monotherapies and in combination with MTX in a rat model of adjuvant arthritis (AA).
The primary objective is to evaluate how these bioactive substances modulate the crosstalk between inflammation and metabolic dysfunction. The study specifically monitors the restoration of metabolic homeostasis by analyzing parameters of oxidative stress, pro-inflammatory cytokines, and lipid metabolism profiles. A focal point of the research is the role of ketone bodies. As endogenous signaling molecules with potent anti-inflammatory properties, the study assesses whether paraxanthine and NO-FAs influence ketogenesis or synergize with ketone-driven pathways to suppress joint pathology.
By correlating changes in lipid metabolism with clinical arthritis scores, this work aims to demonstrate that targeting metabolic checkpoints can enhance the efficacy of MTX. This suggests a novel pharmacological strategy to induce favorable immuno-metabolic reprogramming, potentially allowing for dose reduction of cytostatic drugs and minimizing systemic toxicity.