Skip to main content

Advertisement

SpringerLink
Log in

Comparative evaluation of therapeutic efficacy of intra-articular oxaceprol with conventional modalities in osteoarthritis animal model

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The duration and dose-dependent side effects of conventional intra-articular corticosteroid treatment in osteoarthritis (OA) like cartilage damage and chondrocyte toxicity warrant the search for alternative therapeutics. Oxaceprol, a recognized oral therapeutic agent for osteoarthritis, is yet to be explored for its intra-articular route of administration confirming better safety profile. In this study, a comparative evaluation of intra-articular oxaceprol and corticosteroid is carried out in osteoarthritis rabbit model. Osteoarthritis was induced by monosodium iodoacetate in rabbits. After randomization into three groups of five animals each: OA with intra-articular injection of saline, OA with intra-articular injection of oxaceprol, and OA with intra-articular injection of corticosteroids, treatment efficacy was analyzed by evaluation of inflammation through knee swelling, pain assessment by wire walking, and hot plate method. Further biopsies were collected for histological characterization. Intra-articular oxaceprol and corticosteroids reduced 20.5 and 24.5% knee swelling respectively within 4 weeks compared to those in control osteoarthritic rabbits. Oxaceprol exhibited analgesic action in visual analogue scoring of wire walking method. Hot plate test further confirmed drastic minimization of pain in oxaceprol intervention. Histological investigation suggested that application of oxaceprol has the abilities to protect articular cartilages from degenerative changes that occur in osteoarthritis. Marked improvement both in bone and cellular matrixes was observed in oxaceprol-treated group while gross lesions were visible and consisted of a well-demarcated area of cartilage erosion in control group. Intra-articular injection of oxaceprol showed remarkable improvement of articular cartilage in chemically induced osteoarthritic rabbits.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Plotnikoff R, Karunamuni N, Lytvyak E, Penfold C, Schopflocher D, Imayama I, Johnson ST, Raine K (2015) Osteoarthritis prevalence and modifiable factors: a population study. BMC Public Health 15(1):1195

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jonsson H, Olafsdottir S, Sigurdardottir S, Aspelund T, Eiriksdottir G, Sigurdsson S, Harris TB, Launer L, Gudnason V (2016) Incidence and prevalence of total joint replacements due to osteoarthritis in the elderly: risk factors and factors associated with late life prevalence in the AGES-Reykjavik Study. BMC Musculoskelet Disord 17(1):14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Blanco FJ, Guitian R, Vázquez-Martul E, de Toro FJ, Galdo F (1998) Osteoarthritis chondrocytes die by apoptosis: a possible pathway for osteoarthritis pathology. Arthritis Rheumatol 41(2):284–289

    Article  CAS  Google Scholar 

  4. Henrotin Y, Gharbi M, Dierckxsens Y, Priem F, Marty M, Seidel L, Albert A, Heuse E, Bonnet V, Castermans C (2014) Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial. BMC Complement Altern Med 14(1):159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Gelber AC (2015) Conventional medical therapy for osteoarthritis: current state of the evidence. Curr Opin Rheumatol 27(3):312–317

    Article  PubMed  CAS  Google Scholar 

  6. Herrmann G, Steeger D, Klasser M, Wirbitzky J, Fürst M, Venbrocks R, Rohde H, Jungmichel D, Hildebrandt H, Parnham M (2000) Oxaceprol is a well-tolerated therapy for osteoarthritis with efficacy equivalent to diclofenac. Clin Rheumatol 19(2):99–104

    Article  PubMed  CAS  Google Scholar 

  7. Chia SL, Sawaji Y, Burleigh A, McLean C, Inglis J, Saklatvala J, Vincent T (2009) Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis. Arthritis Rheumatol 60(7):2019–2027

    Article  CAS  Google Scholar 

  8. Shah J, Mirza N, Patel V (2014) A comparative study for safety and efficacy of oxaceprol and diacerein in osteoarthritis of knee joints. PharmaTutor 2(6):108–114

    Google Scholar 

  9. Kruger K, Klasser M, Mossinger J, Becker U (2007) Oxaceprol—a randomised, placebo-controlled clinical study in osteoarthritis with a non-conventional non-steroidal anti-inflammatory drug. Clin Exp Rheumatol 25(1):29–34

    PubMed  CAS  Google Scholar 

  10. Witte S, Lasek R, Victor N (2002) Meta-analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis

  11. Gu J, Chen N, Ding G, Zhang Z (2011) Determination of oxaceprol in rat plasma by LC–MS/MS and its application in a pharmacokinetic study. J Pharm Biomed Anal 54(1):173–178

    Article  PubMed  CAS  Google Scholar 

  12. Kim J, Lee EY, Koh E-M, Cha H-S, Yoo B, Lee CK, Lee YJ, Ryu H, Lee KH, Song YW (2009) Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, phase IV study in Korean patients. Clin Ther 31(12):2860–2872

    Article  PubMed  CAS  Google Scholar 

  13. Riera H, Barbara A, Aprile F, Maheu E, Mitrovic D (1989) Effect of oxaceprol on the synthesis and degradation in vitro of proteoglycans and proteins by calf articular cartilage explants. Revue du rhumatisme et des maladies osteo-articulaires 57(7–8):579–583

    Google Scholar 

  14. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G (2005) Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev 2

  15. Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M (2011) Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy: J Arthrosc Relat Surg 27(11):1490–1501

    Article  Google Scholar 

  16. Lo GH, LaValley M, McAlindon T, Felson DT (2003) Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA 290(23):3115–3121

    Article  PubMed  CAS  Google Scholar 

  17. Sampson S, Gerhardt M, Mandelbaum B (2008) Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med 1(3–4):165–174

    Article  PubMed  PubMed Central  Google Scholar 

  18. Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A (2012) Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil 91(5):411–417

    Article  PubMed  Google Scholar 

  19. Singh H, Francis N, Mitra A (2015) Current trends in osteoarthritis management—a short review. Medicine 3

  20. Bajpayee AG, Wong CR, Bawendi MG, Frank EH, Grodzinsky AJ (2014) Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis. Biomaterials 35(1):538–549

    Article  PubMed  CAS  Google Scholar 

  21. Sarkar S, Mukhopadhyay A, Chaudhary A, Rajput M, Pawar HS, Mukherjee R, Das AK, Banerjee P, Chatterjee J (2017) Therapeutic interfaces of honey in diabetic wound pathology. Wound Med 18:21–32. https://doi.org/10.1016/j.wndm.2017.07.001

    Article  Google Scholar 

  22. Förster K (2000) Drug treatment of osteoarthritis: clinical aspects. Osteoarthritis Berlin Heidelberg New York: Springer-Verlag 66–81

  23. Schuelert N, McDougall JJ (2009) Grading of monosodium iodoacetate-induced osteoarthritis reveals a concentration-dependent sensitization of nociceptors in the knee joint of the rat. Neurosci Lett 465(2):184–188

    Article  PubMed  CAS  Google Scholar 

  24. Ionac M, Parnham M, Plauchithiu M, Brune K (1996) Oxaceprol, an atypical inhibitor of inflammation and joint damage. Pharmacol Res 33(6):367–373

    Article  PubMed  CAS  Google Scholar 

  25. Chattopadhyay H, Auddy B, Sur T, Sana S, Datta S (2016) Accentuated transdermal application of glucosamine sulphate attenuates experimental osteoarthritis induced by monosodium iodoacetate. J Mater Chem B 4(25):4470–4481

    Article  CAS  Google Scholar 

  26. Andersen ML, Santos EH, Maria de Lourdes VS, da Silva AA, Tufik S (2004) Evaluation of acute and chronic treatments with Harpagophytum procumbens on Freund’s adjuvant-induced arthritis in rats. J Ethnopharmacol 91(2):325–330

    Article  PubMed  Google Scholar 

  27. Das RK, Anura A, Pal M, Bag S, Majumdar S, Barui A, Chakraborty C, Ray AK, Sengupta S, Paul RR (2013) Epithelio-mesenchymal transitional attributes in oral sub-mucous fibrosis. Exp Mol Pathol 95(3):259–269

    Article  PubMed  CAS  Google Scholar 

  28. Ostergaard K, Andersen CB, Petersen J, Bendtzen K, Salter DM (1999) Validity of histopathological grading of articular cartilage from osteoarthritic knee joints. Ann Rheum Dis 58(4):208–213

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Sarkar S, Chaudhary A, Saha TK, Das AK, Chatterjee J (2018) Modulation of collagen population under honey assisted wound healing in diabetic rat model. Wound Med 20:7–17. https://doi.org/10.1016/j.wndm.2017.12.001

    Article  Google Scholar 

  30. Pawar HS, Francis NK, Rameshbabu AP, Dhara S (2016) 2,5-Dihydro-2,5-dimethoxyfuran crosslinked silk-chitosan blend tubular construct for vascular graft application. Materials Today Commun 8:139–147. https://doi.org/10.1016/j.mtcomm.2016.07.005

    Article  CAS  Google Scholar 

  31. Harris A, Schropp A, Messmer K (1998) Effects of oxaceprol on the microcirculation in ischemia/reperfusion injury. Eur J Med Res 3(4):182–188

    PubMed  CAS  Google Scholar 

  32. Lachmann G, Siegemund B, Kusche W (1990) Pharmacokinetics and metabolism of 14C-oxaceprol in beagle dogs after intramuscular and oral administration. Arzneimittelforschung 40(2 Pt 1):200–206

    PubMed  CAS  Google Scholar 

  33. Riera H, Aprile F, Mitrovic D (1991) Effet de l’oxacéprol sur la structure des protéoglycannes synthétisés par les chondrocytes articulaires de veau. Revue du rhumatisme et des maladies ostéo-articulaires 58(9):629–634

    PubMed  CAS  Google Scholar 

  34. Collins JE, Losina E, Nevitt MC, Roemer FW, Guermazi A, Lynch JA, Katz JN, Kent Kwoh C, Kraus VB, Hunter DJ (2016) Semiquantitative imaging biomarkers of knee osteoarthritis progression: data from the Foundation for the National Institutes of health osteoarthritis biomarkers consortium. Arthritis Rheumatol 68(10):2422–2431

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Cone K, Krivitsky R, Warner E, Imbert I, Allen J, Henderson T, Rosen CJ, Bilsky EJ, King T, Stevenson GW (2016) Effects of MIA-induced osteoarthritis on hind limb weight bearing and bone biology endpoints in rats with or without access to running wheels. FASEB J 30(1 Supplement):928.923

    Google Scholar 

Download references

Acknowledgements

We acknowledge the resource support from Dr. Anjan Adhikari, Associate Professor, Department of Pharmacology, R.G. Kar Medical College, Kolkata. We are also thankful to IIT Kharagpur for infrastructural support.

Author information

Authors and Affiliations

  1. National JALMA Institute for Leprosy & Other Mycobacterial Diseases (ICMR), Agra, India

    Harpreet Singh Pawar

  2. Indian Institute of Technology, Kharagpur, India

    Nimmy Kanichai Francis, Tushar Hota, Nabam Peter & Analava Mitra

Authors
  1. Harpreet Singh Pawar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nimmy Kanichai Francis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tushar Hota
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nabam Peter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Analava Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Harpreet Singh Pawar.

Ethics declarations

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pawar, H.S., Francis, N.K., Hota, T. et al. Comparative evaluation of therapeutic efficacy of intra-articular oxaceprol with conventional modalities in osteoarthritis animal model. Clin Rheumatol 37, 2195–2201 (2018). https://doi.org/10.1007/s10067-018-4087-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-018-4087-1

Keywords

Search

Navigation