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Published on: May 16, 2019
Anti-epileptic drugs inhibit viability of synoviocytes in vitro
Jolanta Parada-Turska1, Patrycja Nowicka-Stążka, Maria Majdan
1Department of Rheumatology and Connective Tissue Diseases, Medical University, Lublin, Poland.
Introduction And Objective:
The hyperplasia of synovial fibroblasts is considered to be essential for the evolution of joint destruction in rheumatoid arthritis (RA). Previously, we reported that anti-rheumatic drugs, both COX inhibitors and disease-modifying anti-rheumatic drugs inhibit proliferation of synoviocytes in vitro. The presented study investigates the effect of anti-epileptic drugs on the viability and proliferation of synovial fibroblasts in vitro.
Methods:
Experiments were conducted on human synoviocytes derived from an RA patient and rabbit synoviocytes cell line HIG-82. Cell proliferation and viability were assessed by means of BrdU assay and MTT assay, respectively. The IC50 value (the concentration of drug necessary to induce 50% inhibition) together with confidence limits was calculated.
Results:
Carbamazepine inhibited proliferation of human fibroblasts and viability of HIG-82 with IC 50 values of 86 µM and 82 µM, respectively. Diphenylhydantoin, valproate and phenobarbital inhibited viability of HIG-82 cells with the IC50 values of 110, 500 and 1031 µM, respectively.
Conclusion:
Based on these findings, it can be suggested that anti-epileptic drugs may have a disease-modifying effect on rheumatoid synovial proliferation.
Insights
Certain anti-epileptic drugs show potential in treating rheumatoid arthritis (RA) by inhibiting the proliferation of synovial fibroblasts. This suggests a possible disease-modifying effect for these drugs in RA management.
Area of Science:
- Rheumatology
- Pharmacology
- Cell Biology
Background:
- Synovial fibroblast hyperplasia is a key factor in rheumatoid arthritis (RA) joint destruction.
- Previously, anti-rheumatic drugs were shown to inhibit synoviocyte proliferation in vitro.
- The therapeutic potential of anti-epileptic drugs (AEDs) in RA remains largely unexplored.
Purpose of the Study:
- To investigate the in vitro effects of AEDs on the viability and proliferation of synovial fibroblasts.
- To determine the efficacy of specific AEDs in inhibiting rheumatoid arthritis synovial cell growth.
Main Methods:
- Experiments utilized human rheumatoid arthritis (RA) synoviocytes and the HIG-82 rabbit synoviocyte cell line.
- Cell proliferation was assessed using the BrdU assay, and cell viability was measured by the MTT assay.
- The IC50 values, representing the drug concentration for 50% inhibition, were calculated for each tested AED.
Main Results:
- Carbamazepine demonstrated significant inhibition of human fibroblast proliferation (IC50: 86 µM) and HIG-82 cell viability (IC50: 82 µM).
- Other AEDs, including diphenylhydantoin, valproate, and phenobarbital, also inhibited HIG-82 cell viability with varying IC50 values (110 µM, 500 µM, and 1031 µM, respectively).
Conclusions:
- The findings suggest that certain AEDs possess anti-proliferative properties against rheumatoid arthritis synovial fibroblasts.
- AEDs may represent a novel class of disease-modifying agents for rheumatoid arthritis.
- Further research is warranted to explore the clinical application of AEDs in RA treatment.
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