Preclinical efficacy of a gastro-sparing novel thiazolidin-4-one in alleviating secondary lesions of polyarthritis: A multi-parametric approach.
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.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104, Karnataka, India.
Jayesh
J
Mudgal
Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104, Karnataka, India.
Vasantharaju S
VS
Gowdra
Department of Virus Research (Manipal Centre for Virus Research), Manipal University, Manipal 576 104, Karnataka, India.
Piya P
PP
Mudgal
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104, Karnataka, India.
Pawan G
PG
Nayak
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104, Karnataka, India.
Nitesh
N
Kumar
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104, Karnataka, India.
Zenab
Z
Attari
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104, Karnataka, India.
C Mallikarjuna
CM
Rao
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104, Karnataka, India. Electronic address: ng.kutty@manipal.edu.
Gopalan K
GK
Nampurath
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D033023:Foot Joints / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D005753:Gastric Mucosa / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D010146:Pain / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011859:Radiography; D017207:Rats, Sprague-Dawley; D053778:Thiazolidines / Q000494:pharmacology / Q000627:therapeutic use*; D014110:Touch; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone
Analgesic; Anti-inflammatory; Cytokines; Gastro-sparing; Prostaglandin; Thiazolidin-4-one