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

Jayesh Mudgal, Vasantharaju S. Gowdra, Piya P. Mudgal, Pawan G. Nayak, Nitesh Kumar, Zenab Attari, C. Mallikarjuna Rao, Gopalan K. Nampurath

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2 Citations (Scopus)

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 rats were 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 cardiovascular 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 metabolism by 4C was 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.

Original languageEnglish
Pages (from-to)74-83
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Volume91
DOIs
Publication statusPublished - 25-08-2016

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Arthritis
Experimental Arthritis
Cytokines
Dinoprostone
Stomach
Inflammation
Kidney
Pain
Diclofenac
Liver
Therapeutic Uses
Prostaglandins
Sprague Dawley Rats
Disease Progression
Interleukin-6
Blood Cells
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Joints
Safety

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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title = "Preclinical efficacy of a gastro-sparing novel thiazolidin-4-one in alleviating secondary lesions of polyarthritis: A multi-parametric approach",
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 rats were 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 cardiovascular 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 metabolism by 4C was 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.",
author = "Jayesh Mudgal and Gowdra, {Vasantharaju S.} and Mudgal, {Piya P.} and Nayak, {Pawan G.} and Nitesh Kumar and Zenab Attari and Rao, {C. Mallikarjuna} and Nampurath, {Gopalan K.}",
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AU - Gowdra, Vasantharaju S.

AU - Mudgal, Piya P.

AU - Nayak, Pawan G.

AU - Kumar, Nitesh

AU - Attari, Zenab

AU - Rao, C. Mallikarjuna

AU - Nampurath, Gopalan K.

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