OBJECTIVETo study the role of tranilast in the pathogenesis of myocardiac fibrosis in viral myocarditis.

METHODSSeventy-two BALB/C mice were randomly divided into control, model and intervention groups (n=24 each). Mice in the model and intervention groups were infected with Coxsackievirus B3 to induce viral myocarditis. The intervention group was given with tranilast (200 mg/kg) by gavage until sacrifice for sampling, while the other two groups were administered with the same volume of normal saline. Cardiac tissues were obtained from 8 mice on 7, 14 and 28 days after modeling. The mast cell number was observed by toluidine blue staining and thionine staining. The cardiac tissues were stained with hematoxylin and eosin as well as masson trichrome to observe the pathological changes in cardiac tissues. The mRNA and protein expression of osteopontin and transforming growth factor-β1 was measured by RT-PCR and immunohistochemistry respectively.

RESULTSIn the model group, the mRNA and protein expression of osteopontin reached the highest level on the 7th day, decreasing from the 14th day, and became to the least on the 28th day; while the expression of TGF-β1 increased from the 7th day, reaching a peak on the 14th day, and decreased slightly on the 28th day. The mRNA and protein expression of TGF-β1 and OPN was lower in the intervention group than the model group (P<0.05), but higher than the control group (P<0.05). The expression of OPN mRNA was positively correlated to the number of mast cells.

CONCLUSIONSTranilast can reduce myocardial fibrosis by decreasing the number of mast cells, inhibiting the expression of TGF-β1 and OPN.

Animals ; Fibrosis ; Male ; Mast Cells ; drug effects ; Mice ; Mice, Inbred BALB C ; Myocarditis ; complications ; Myocardium ; pathology ; Osteopontin ; analysis ; genetics ; Transforming Growth Factor beta1 ; analysis ; genetics ; ortho-Aminobenzoates ; pharmacology ; therapeutic use

PURPOSE: Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to exhibit antitumor effects in various cancers apart from nasopharyngeal cancer (NPC). NPC exhibits high invasiveness, as well as metastatic potential, and patients continue to suffer from residual, recurrent, or metastatic disease even after chemoradiation therapy. Therefore, new treatment strategies are needed for NPC. In this study, we investigated the efficacy and molecular mechanisms of TA in NPC treatment. MATERIALS AND METHODS: TA-induced cell death was detected by cell viability assay in the NPC cell lines, HNE1 and HONE1. Wound healing assay, invasion assay, and Western blot analysis were used to evaluate the antitumor effects of TA in NPC cell lines. RESULTS: Treatment with TA suppressed the migration and invasion of HNE1 and HONE1 cells. Hepatocyte growth factor enhanced the proliferation, migration, and invasion abilities of NPC cells. This enhancement was successfully inhibited by TA treatment. Treatment with TA increased phosphorylation of p38, and the inhibition of p38 with SB203580 reversed the cytotoxic, anti-invasive, and anti-migratory effects of TA treatment in NPC cell lines. Moreover, inhibition of p38 also reversed the decrease in expression of Slug that was induced by TA treatment. CONCLUSION: In conclusion, the activation of p38 plays a role in mediating TA-induced cytotoxicity and inhibition of invasion and migration via down-regulation of Slug.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use ; Cell Line, Tumor ; Cell Movement/*drug effects ; Cell Proliferation/*drug effects ; Cell Survival/*drug effects ; Down-Regulation ; Gastropoda ; Gene Expression Regulation, Neoplastic/drug effects ; Hepatocyte Growth Factor/metabolism/*pharmacology ; Humans ; Imidazoles ; MAP Kinase Signaling System/drug effects ; Nasopharyngeal Neoplasms/*drug therapy/metabolism/pathology ; Neoplasm Invasiveness/*prevention & control ; Phosphorylation/drug effects ; Pyridines ; ortho-Aminobenzoates/*pharmacology/therapeutic use