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A single intra-articular dose of vitamin D analog calcipotriol alleviates synovitis without adverse effects in rats.
- Source :
-
PloS one [PLoS One] 2021 Apr 20; Vol. 16 (4), pp. e0250352. Date of Electronic Publication: 2021 Apr 20 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- 1,25-dihydroxyvitamin-D3 and its derivatives have shown anti-arthritic and chondroprotective effects in experimental animal models with prophylactic dosing. The purpose of this preliminary study was to test the efficacy and safety of calcipotriol, vitamin D analog, as a treatment for a fully-developed knee arthritis in Zymosan-induced arthritis (ZIA) model. Forty 5-month-old male Sprague-Dawley rats were randomized into three arthritis groups and a non-arthritic control group with no injections (10 rats/group). A day after Zymosan (0.1 mg) had been administrated into the right knee joints, the same knees were injected with calcipotriol (0.1 mg/kg), dexamethasone (0.1 mg/kg) or vehicle in a 100 μl volume. The left control knees were injected with saline (PBS) on two consecutive days. All injections, blood sampling and measurements were performed under general anesthesia on days 0, 1, 3 and 8. Internal organs and knees were harvested on day 8 and the histology of the whole knees was assessed blinded. Joints treated with calcipotriol showed a milder histological synovitis than those treated with vehicle (p = 0.041), but there was no statistically significant difference between the dexamethasone and vehicle groups. The clinical severity of arthritis did not differ between the arthritis groups measured by body temperature, swelling of the knee, thermal imaging, clinical scoring or cytokine levels on days 1, 3 and 8. Weight loss was bigger in rats treated with dexamethasone, propably due to loss of appetite,compared to other arthritis groups on days 2-3 (p<0.05). Study drugs did not influence serum calcium ion and glucose levels. Taken together, this preliminary study shows that a single intra-articular injection of calcipotriol reduces histological grade of synovitis a week after the local injection, but dexamethasone did not differ from the vehicle. Calcipotriol may have an early disease-modifying effect in the rat ZIA model without obvious side effects.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Arthritis, Experimental blood
Arthritis, Experimental chemically induced
Arthritis, Experimental pathology
Blood Glucose metabolism
Calcitriol pharmacology
Calcium blood
Cartilage, Articular drug effects
Cartilage, Articular metabolism
Cartilage, Articular pathology
Dexamethasone pharmacology
Drug Administration Schedule
Hindlimb
Injections, Intra-Articular
Male
Rats
Rats, Sprague-Dawley
Synovitis blood
Synovitis chemically induced
Synovitis pathology
Treatment Outcome
Zymosan administration & dosage
Anti-Inflammatory Agents pharmacology
Arthritis, Experimental drug therapy
Calcitriol analogs & derivatives
Synovitis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 33878143
- Full Text :
- https://doi.org/10.1371/journal.pone.0250352