Anti-inflammatory and ulcerogenic activities of thiazolidine-4-ones in rats
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20185155Keywords:
Anti-inflammatory, Diclofenac, Nimesulide, NSAIDs, Thiazolidine-4-ones, UlcerogenicityAbstract
Background: NSAIDS are associated with side effects and research should continue for developing safer drugs. This study aims to evaluate newer thiazolidine-4-ones for their anti-inflammatory and ulcerogenic activities in wister rats.
Methods: Five groups of wister rats, 6 in each were used. Anti-inflammatory and ulcerogenic activities of diclofenac (30mg/kg), nimesulide (50mg/kg), thia-1 (50mg/kg) and thia-2 (50mg/kg) are compared with control group (4% Gum Acacia). Carrageenin-induced paw edema, formaline induced acute peritonitis and cotton pellet-induced granulomatous tissue formation models were used for evaluating anti-inflammatory activity. After removing cotton pellets with granuloma on 8th day gastric ulcerogenicity was assessed by using macroscopic and microscopic scoring of ulcers.
Results: Diclofenac, nimesulide and thia 2 reduced both paw edema and peritoneal exudate volume significantly (p <0.01). Wet weight of cotton pellets reduced significantly (p <0.01) by diclofenac, nimesulide and thia 2. Diclofenac (p <0.01) and thia 2 (p <0.05) reduced dry weight of cotton pellets significantly. nimesulide and thia-1 reduced it by 19.14% and 2.68% respectively and was considered statistically not significant (p>0.05). Nimesulide, thia-1 and thia-2 did not increase gastric ulcer score significantly (p >0.05). Diclofenac increased ulcer score significantly (p <0.01).
Conclusions: Thia-2 demonstrated significant anti-inflammatory activity in acute and chronic models. In addition to inhibition of cyclooxygenase pathway, PPAR agonistic activity may be involved in its anti-inflammatory activity. No significant ulcerogenicity was observed on comparing with nimesulide and control. Further in-vitro and in-vivo studies are recommended to confirm the results of this study.
References
Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MN. The crucial roles of inflammatory mediators in inflammation: a review. Veterinary World. 2018 May;11(5):627-35.
Bagad AS, Joseph JA, Bhaskaran N, Agarwal A. Comparative evaluation of anti-inflammatory activity of curcuminoids, turmerones, and aqueous extract of Curcuma longa. Adv Pharmacol Sci. 2013;2013.
Hawkins C, Hanks GW. The gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs: a review of the literature. J Pain Symptom Manage. 2000 Aug;20(2):140-51.
Thabrew MI, Arawwawala LDAM. An overview of in-vivo and In-vitro models that can be used for evaluating anti-gastric ulcer potential of medicinal plants. Austin Biol. 2016;1(2):1007
Madhuri AS, Mohanvelu R, Ramabhimaiah S. Evaluation of anti-inflammatory activity of aqueous extract of Mangifera indica leaves in albino rats. Int J Basic Clin Pharmacol. 2016 Dec 30;5(3):635-8.
Venerito M, Wex T, Malfertheiner P. Nonsteroidal anti-inflammatory drug-induced gastroduodenal bleeding: risk factors and prevention strategies. Pharmaceuticals. 2010 Jul 14;3(7):2225-37.
Faizan S, Abdul S, Akram MD. Analgesic and anti-inflammatory activity of new substituted Thiazolidin-4-One Derivatives. Indo Am J P Sci. 2017:4(08);2461-72.
de Magalhães LR, Alves IB, dos Santos E, da Silva VB, da Silva LC, da Silva AL, et al. Activity anti-inflammatory and in silico study of new thiazolidinedione derivatives. Br J Pharmaceut Res. 2014 Jul 15;4(14):1739.
Shiva MN, Srinivasa V. Screening of new synthetic thiazolidine-4-ones for anti-inflammatory activity in albino rats. Indian J Pharmacol. 2003 Jan 1;35(1):61.
Sushma M, Sudha S, Shivamurthy N, Venkataraman BV. Analgesic activity of new synthetic thiazolidine-4-ones derivatives. Indian J Experimental Biol 2004;42:812-5.
Buttle GA, D'arcy PF, Howard EM, Kellett DN. Plethysmometric measurement of swelling in the feet of small laboratory animals. Nature. 1957 Mar;179(4560):629.
Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proceedings Soc Exp Biol Med. 1962 Dec;111(3):544-7.
Teotino UM, Friz LP, Gandini A, Bella DD. Thio derivatives of 2, 3-dihydro-4H-1, 3-benzoxazin-4-one. Synthesis and pharmacological properties. J Medicin Chem. 1963 May;6(3):248-50.
Swingle KF, Shideman FE. Phases of the inflammatory response to subcutaneous implantation of a cotton pellet and their modification by certain antiinflammatory agents. J Pharmacol Experiment Therapeut. 1972 Oct 1;183(1):226-34.
Ochi T, Goto T. Anti-inflammatory activity of a novel selective cyclooxygenase-2 inhibitor, FR140423, on type II collagen-induced arthritis in Lewis rats. Prostaglandins Other Lipid Mediators. 2001 Dec 1;66(4):317-27.
Jain NK, Singh A, Kulkarni SK. Analgesic, anti‐inflammatory and ulcerogenic activity of a zinc‐naproxen complex in mice and rats. Pharmacy Pharmacol Communications. 1999 Oct;5(10):599-602.
De Leval X, Henrotin Y, Labasse A, Reginster JY, Neven P, Delarge J, et al. Comparison of the Effects of Nimesulide and Nimesulide‐L‐lysine on PGE2 Production by COX‐1 and COX‐2 and on Chondrocyte Metabolism In‐vitro. Pharmacy Pharmacol Communications. 2000 Feb;6(2):83-7.
Kamble S, Ahmed MZ, Ramabhimaiaha S, Patil P. Anti-inflammatory activity of Raphanus sativus L in acute and chronic experimental models in Albino rats. Biomed Pharmacol J. 2013;6(2):315-20.
Sharma V, Laxmi V, Chauhan S. Cyclooxygenase-3: a review. Am J Pharm Tech Res. 2012;2(3):236-42
Batlouni M. Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects. Brazilian Arch Cardiol. 2010 Apr; 94 (4): 556-63.
Dhikav V, Singh S, Pande S, Chawla A, Anand KS. Non-steroidal drug-induced gastrointestinal toxicity: mechanisms and management. J Indian Acad Clin Med. 2003 Oct;4(4):315-22.
Rosenbloom D, Craven MA. A review of non-steroidal anti-inflammatory drugs. Canad Fam Physician. 1983 Nov;29:2121.
Veloso CC, Cabral LD, Bitencourt AD, Franqui LS, Santa-Cecília FV, Dias DF, et al. Anti-inflammatory and antinociceptive effects of the hydroethanolic extract of the flowers of Pyrostegia venusta in mice. Braz J Pharmacognosy. 2012 Feb;22(1):162-8.
Verdam MC, Guilhon-Simplicio F, Andrade KC, Fernandes KL, Machado TM, da Silva FM, et al. Analgesic, anti-inflammatory, and antioxidant activities of Byrsonima duckeana WR Anderson (Malpighiaceae). Scientific World J. 2017;2017.
Borges JC, de Sousa Aguiar RW, de Sousa JE, Ripardo Filho HS, Guilhom GS, Santos LS, et al. Anti-inflammatory and non ulcerogenic activities of acetylbergenin. Afr J Pharmacy Pharmacol. 2017 Sep 8;11(33):402-10.
Bhuvana KB, Hema NG. An evaluation of Aloe Vera for its acute anti-inflammatory activity in rat peritonitis model. World J Pharmaceut Res. 2014;3(3):4508-19
Rosa MD, Willoughby DA. Screens for anti‐inflammatory drugs. J Pharmacy Pharmacol. 1971 Apr;23(4):297-8.
Ramakrishnan G, Joshua AJ, Goudar K, Amit A. Comparative evaluation of anti-inflammatory activity of different extracts of Boswellia serrata in Wistar Albino rats. Int J of PharmTech Res. 2011;3(1):261-7
Sharma GN, Dubey SK, Sati N, Sanadya J. Ulcer healing potential of Aegle marmelos fruit seed. Asian J Pharm Life Sci. 2011 Mar;1(2):172-8.
Hawkey CJ. COX-2 inhibitors. Lancet. 1999 Jan 23;353(9149):307-14.
Walz DT, DiMartino MJ, Misher A. Adjuvant-induced arthritis in rats. II. Drug effects on physiologic, biochemical and immunologic parameters. J Pharmacol Exp Therapeut. 1971 Jul 1;178(1):223-31.