Preclinical efficacy of a gastro-sparing novel thiazolidin-4-one in alleviating secondary lesions of polyarthritis: A multi-parametric approach

Mudgal, Jayesh and Gowdra, Vasantharaju S and Mudgal, Piya Paul and Nayak, Pawan G and Kumar, Nitesh and Attari, Zenab and Rao, Mallikarjuna C and Nampurath, Gopalan Kutty (2016) Preclinical efficacy of a gastro-sparing novel thiazolidin-4-one in alleviating secondary lesions of polyarthritis: A multi-parametric approach. European Journal of Pharmaceutical Sciences, 91. pp. 74-83. ISSN 0928-0987

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Abstract

The promising role of thiazolidin-4-ones (TZOs) against inflammatory conditions has been reported. From our lab, one of the TZO derivatives, compound 4C, exerted anti-inflammatory potential via inhibition of locally released cytokines and prostaglandin. In continuance, a detailed study was undertaken for the preclinical profiling of this promising TZO derivative against polyarthritis in rats, along with assessment of risk associated with the treatment. Male Sprague-Dawley ratswere used for the adjuvant-induced arthritis (AIA) model. Based on the development of secondary lesion, the animals were randomized into different treatment groups. To establish the efficacy of the test compound, parameters such as inflammation, pain, disease progression, cytokines and prostaglandin (PG)-E2 levels and complete blood cell profile were recorded along with radiological and histological examinations of joints. The study also focused on evaluating the side effect of test compound on gastric, liver, renal, blood and cardiovas ular components. Compound 4C exerted promising therapeutic effect against secondary lesions in polyarthritis in rats. It limited the progression of chronic inflammation and associated pain in rats. Modulation of cytokine signalling and arachidonate metabolismby 4Cwas evident from inhibition of interleukin (IL)-6, tumor necrosis factor (TNF)-α and PGE2 generation in AIA rats. Comparatively, compound 4C was safer than diclofenac to cause gastric, liver, renal, blood and cardiovascular toxicities. These finding supports the efficacy and safety profile of 4C, a TZO derivative in limiting the progression of arthritis when administered orally.

Item Type: Article
Uncontrolled Keywords: Thiazolidin-4-one; cytokines; prostaglandin; analgesic; Anti-inflammatory; Gastro-sparing.
Subjects: Departments at MU > Manipal Centre for Virus Research
Pharmacy > MCOPS Manipal > Pharmaceutical Quality Assurance
Pharmacy > MCOPS Manipal > Pharmaceutics
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 29 Jun 2016 16:14
Last Modified: 29 Jun 2016 16:14
URI: http://eprints.manipal.edu/id/eprint/146439

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