Abstract
Objectives To study the chondroprotective and anti-inflammatory potential of inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea (SMT) in in-vitro model. Methods Rabbit cartilage explants were stimulated with recombinant human interleukin 1β (rhIL-1β), and the chondroprotective and anti-inflammatory effects of SMT were investigated. Rat synovial explants were stimulated with LPS, and the anti-inflammatory effect of SMT on synovium was studied. To examine the role of SMT in synovial inflammation mediated cartilage damage, LPS stimulated synovial explants were cultured with dead cartilage with or without SMT for 72 h. The culture medium was analysed for sulfated glycosaminoglycans (GAGs) and hydroxyproline as measure of proteoglycans and collagen degradation, respectively. Key findings SMT significantly reduced GAGs, hydroxyproline, matrix metalloproteinase (MMP)-13, tumour necrosis factor alpha (TNF-α), prostaglindin E2 (PGE2) and nitrite release in stimulated rabbit cartilage media indicating chondroprotective and anti-inflammatory effects of SMT in osteoarthritis (OA). Stimulated synovial explants caused release of nitrite, PGE2, IL-1β and TNF-α in the medium which were significantly reduced by SMT indicating its anti-inflammatory action. SMT significantly reduced GAGs and hydroxyproline in medium and shown protective effect against synovium-mediated cartilage damage. Conclusions SMT inhibited cartilage degradation, synovial inflammation and synovium-mediated cartilage damage, suggesting that SMT may be an agent for pharmacological intervention in OA.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1021-1031 |
| Number of pages | 11 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 66 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
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Keywords
- cartilage explants
- osteoarthritis
- S-methylisothiourea
- synovial explants
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Medicine(all)
Cite this
Chondroprotective and anti-inflammatory effects of S-methylisothiourea, an inducible nitric oxide synthase inhibitor in cartilage and synovial explants model of osteoarthritis. / Balaganur, Venkanna; Pathak, Nitya Nand; Lingaraju, Madhu Cholenahalli; More, Amar Sunil; Latief, Najeeb; Kumari, Rashmi Rekha; Kumar, Dinesh; Tandan, Surendra K.
In: Journal of Pharmacy and Pharmacology, Vol. 66, No. 7, 2014, p. 1021-1031.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chondroprotective and anti-inflammatory effects of S-methylisothiourea, an inducible nitric oxide synthase inhibitor in cartilage and synovial explants model of osteoarthritis
AU - Balaganur, Venkanna
AU - Pathak, Nitya Nand
AU - Lingaraju, Madhu Cholenahalli
AU - More, Amar Sunil
AU - Latief, Najeeb
AU - Kumari, Rashmi Rekha
AU - Kumar, Dinesh
AU - Tandan, Surendra K.
PY - 2014
Y1 - 2014
N2 - Objectives To study the chondroprotective and anti-inflammatory potential of inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea (SMT) in in-vitro model. Methods Rabbit cartilage explants were stimulated with recombinant human interleukin 1β (rhIL-1β), and the chondroprotective and anti-inflammatory effects of SMT were investigated. Rat synovial explants were stimulated with LPS, and the anti-inflammatory effect of SMT on synovium was studied. To examine the role of SMT in synovial inflammation mediated cartilage damage, LPS stimulated synovial explants were cultured with dead cartilage with or without SMT for 72 h. The culture medium was analysed for sulfated glycosaminoglycans (GAGs) and hydroxyproline as measure of proteoglycans and collagen degradation, respectively. Key findings SMT significantly reduced GAGs, hydroxyproline, matrix metalloproteinase (MMP)-13, tumour necrosis factor alpha (TNF-α), prostaglindin E2 (PGE2) and nitrite release in stimulated rabbit cartilage media indicating chondroprotective and anti-inflammatory effects of SMT in osteoarthritis (OA). Stimulated synovial explants caused release of nitrite, PGE2, IL-1β and TNF-α in the medium which were significantly reduced by SMT indicating its anti-inflammatory action. SMT significantly reduced GAGs and hydroxyproline in medium and shown protective effect against synovium-mediated cartilage damage. Conclusions SMT inhibited cartilage degradation, synovial inflammation and synovium-mediated cartilage damage, suggesting that SMT may be an agent for pharmacological intervention in OA.
AB - Objectives To study the chondroprotective and anti-inflammatory potential of inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea (SMT) in in-vitro model. Methods Rabbit cartilage explants were stimulated with recombinant human interleukin 1β (rhIL-1β), and the chondroprotective and anti-inflammatory effects of SMT were investigated. Rat synovial explants were stimulated with LPS, and the anti-inflammatory effect of SMT on synovium was studied. To examine the role of SMT in synovial inflammation mediated cartilage damage, LPS stimulated synovial explants were cultured with dead cartilage with or without SMT for 72 h. The culture medium was analysed for sulfated glycosaminoglycans (GAGs) and hydroxyproline as measure of proteoglycans and collagen degradation, respectively. Key findings SMT significantly reduced GAGs, hydroxyproline, matrix metalloproteinase (MMP)-13, tumour necrosis factor alpha (TNF-α), prostaglindin E2 (PGE2) and nitrite release in stimulated rabbit cartilage media indicating chondroprotective and anti-inflammatory effects of SMT in osteoarthritis (OA). Stimulated synovial explants caused release of nitrite, PGE2, IL-1β and TNF-α in the medium which were significantly reduced by SMT indicating its anti-inflammatory action. SMT significantly reduced GAGs and hydroxyproline in medium and shown protective effect against synovium-mediated cartilage damage. Conclusions SMT inhibited cartilage degradation, synovial inflammation and synovium-mediated cartilage damage, suggesting that SMT may be an agent for pharmacological intervention in OA.
KW - cartilage explants
KW - osteoarthritis
KW - S-methylisothiourea
KW - synovial explants
UR - http://www.scopus.com/inward/record.url?scp=84902533543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902533543&partnerID=8YFLogxK
U2 - 10.1111/jphp.12228
DO - 10.1111/jphp.12228
M3 - Article
VL - 66
SP - 1021
EP - 1031
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 7
ER -