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Yadav S.K.,Dr Bc Roy Post Graduate Institute Of Basic Medical Science | Adhikary B.,Dr Bc Roy Post Graduate Institute Of Basic Medical Science | Bandyopadhyay S.K.,Dr Bc Roy Post Graduate Institute Of Basic Medical Science | Chattopadhyay S.,Bhabha Atomic Research Center
Biochimica et Biophysica Acta - General Subjects | Year: 2013

Background The gastro-intestinal disorders, induced by the NSAIDs including indomethacin (IND) remain unresolved medical problems. Herein, we disclose allylpyrocatechol (APC) as a potential agent against IND-gastropathy and rationalize its action mechanistically. Methods Mice were pre-treated with APC for 1 h followed by IND (18 mg kg- 1) administration, and the ulcer-prevention capacity of APC was evaluated on the 3rd day by histology. Its effect on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COX, prostaglandins, growth factors and their receptors) and signaling parameters (NF-κB and MAPKs) were assessed by immunoblots/mRNA, and ELISA at the time points of their maximal changes due to IND administration. Results IND induced oxidative stress, triggering mucosal TNF-α that activated NF-κB and JNK MAPK signaling in mice. These increased the pro-inflammatory biochemical parameters, but reduced the healing factors. APC reversed all the adverse effects to prevent gastric ulceration. APC (5 mg kg- 1), trolox (50 mg kg- 1) and NAC (250 mg kg- 1) showed similar protection that was better than that by misoprostol (5 μg kg- 1) and omeprazole (3 mg kg- 1). Conclusions The anti-ulcer effect of APC can be primarily attributed to its antioxidant action that helped in controlling various inflammatory parameters and augmenting angiogenesis. General significance Given that APC is an effective, non-toxic antioxidant with appreciable natural abundance, further evaluation of its pharmacokinetics and dynamics would help in promoting it as a new anti-inflammatory agent. © 2013 Elsevier B.V. Source


Yadav S.K.,Dr Bc Roy Post Graduate Institute Of Basic Medical Science | Adhikary B.,Dr Bc Roy Post Graduate Institute Of Basic Medical Science | Chand S.,Bhabha Atomic Research Center | Maity B.,Dr Bc Roy Post Graduate Institute Of Basic Medical Science | And 2 more authors.
Free Radical Biology and Medicine | Year: 2012

The probable cross talk among large numbers of inflammatory and angiogenic parameters in indomethacin (IND)-induced gastropathy and the associated signaling mechanism were studied in a mouse model. A single dose of IND (18 mg/kg, po) produced robust gastric ulceration in mice without any mortality, which peaked on the third day, but started healing from the fifth day onward. The ulceration was associated with increased myeloperoxidase activity and expression of proinflammatory (TNF-α, adhesion molecules, COX-2) and antiangiogenic (endostatin) parameters. The levels of proangiogenic factors such as COX-1, prostaglandin E, VEGF, and von Willebrand factor VIII were downregulated by IND. Our results revealed that although the maximal and minimal levels of these parameters were attained sequentially at different time points, TNF-α upregulation was the primary event to initiate and induce gastric ulceration. IND also activated NF-κB and all the MAP kinases, but only the inhibitors of TNF-α, NF-κB, and JNK MAP kinase could abrogate the IND-induced damages. Further TNF-α inhibition also reduced the IND-mediated activation of NF-κB and JNK MAP kinase. All this evidence strongly suggests that mitigation of TNF-α may offer a potential solution to IND-mediated gastropathy. © 2012 Elsevier Inc. Source

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