Background and aim Various drugs have been developed for inflammatory bowel disease (IBD), but still there are limitations in the treatment due to the insufficient responses and significant adverse effects of immunosuppressant. Apocynin is an NADPH-oxidase inhibitor with established safety profiles. We aimed to investigate the protective efficacy of apocynin in IBD using chemical-induced mouse colitis model. Method We induced experimental colitis by administrating 5% dextran sulfate sodium (DSS) to 8-week old BALB/c mouse for 11 days. Apocynin (400 mg/kg) or sulfasalazine (150 mg/kg) were administeredduring7 days. We monitored bodyweight daily and harvested colon and spleen at day 11 to check weight and length. We also examined histopathologic change and pro-, anti-inflammatory cytokines and enzymes from harvested colons (iNOS, COX-2, TNF-α, MCP-1, p-NrF2, and HO-1). Result Apocynin significantly alleviated weight reduction induced by DSS treatment (21.64 ± 0.55 for Apocynin group vs. 20.33 ± 0.90 for DSS group, p = 0.005). Anti-inflammatory efficacy of apocynin was also shown by the recovery of colon weight and length. Histopathologic examination revealed significantly reduced inflammatory foci and erosions by apocynin treatment. Colonic expression of iNOS, COX-2, TNF-α, and MCP-1 was decreased significantly in the apocynin treated group. Anti-inflammatory mediators Nrf2 and HO-1 were activated significantly in apocynin treated mouse. Conclusion Apocynin showed significant anti-inflammatory efficacy against chemically induced colonic inflammation. This study also revealed the unique action of apocynin compared to the currently prescribed drug, sulfasalazine. Given its excellent safety profile and potent efficacy with novel action mechanism, apocynin can be a new therapeutic molecule for the IBD treatment, which can be added to the currently available drugs.

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ABBREVIATIONS: MMP-9, matrix metalloproteinase-9; PI3K, phosphatidylinositol 3-kinase; MAPK, mitogen-activated protein kinase.Received June 7, 2011, Revised August 16, 2011, Accepted August 28, 2011 Corresponding to: Sung-Soo Kim, Department of Pharmacology, College of Medicine, Kangwon National University, Hyoja-2-dong, (Fax) Glioblastoma multiforme is one of the most common and aggressive tumors in central nervous system. It often possesses characteristic necrotic lesions with hemorrhages, which increase the chances of exposure to thrombin. Thrombin has been known as a regulator of MMP-9 expression and cancer cell migration. However, the effects of thrombin on glioma cells have not been clearly understood. In the present study, influences of thrombin on glioma cell migration were examined using Boyden chamber migration assay and thrombin-induced changes in MMP-9 expression were measured using zymography, semi-quantitative RT-PCR, and W estern blotting. Furthermore, underlying signaling pathways by which thrombin induces MMP-9 expression were examined. Thrombin-induced migration and MMP-9 expression were significantly potentiated in the presence of wortmannin, a PI3K inhibitor, whereas MAPK inhibitors suppressed thrombin-induced migration and MMP-9 expression in C6 glioma cells. The present data strongly demonstrate that MAPK and PI3K pathways evidently regulate thrombin-induced migration and MMP-9 expression of C6 glioma cells. Therefore, the control of these pathways might be a beneficial therapeutic strategy for treatment of invasive glioblastoma multiforme.

Objective: The aim of this study was to evaluate generational accumulation of murine fetal ovarian genes following prenatal exposure to 1.765-GHz microwave radiation. Methods: A 1.765-GHz microwave generator was used. Twenty pregnant ICR mice were divided into two groups: the microwave-exposed experimental (irradiated) group, and the sham-exposed (sham) group. On the fifth day post-mating, dam mice were exposed to microwave irradiation in the insulated cage for 8 hours each day. The remaining mice were treated in the same way. Second generation mice were raised for 8 weeks then classified into four groups for examination. We removed the neonatal ovaries on the seventh day after the third delivery. We investigated the expression of six genes in the ovaries: Tnfaip 8, TNFsf 12, Cfd, CCL 11, Zfp 74, and Brd 3. Real time reverse transcription-polymerase chain reaction was performed using total RNA extracted from the removed ovaries. Results: In the third-generation offspring, we detected some differences in ovarian gene expression between the first group and the fourth.Expression of CCL 11, and TNFsf 12 was decreased in the first group compared to the fourth group. Expression of Tnfaip 8, brd 3, Cfd, and Zfp 74 was higher in the first group than in the fourth group. We found differing results when we compared ovarian gene expression in mice of the second generation with those of the third. Conclusion:The results suggest that there is no generational accumulation of murine ovarian genes in offspring exposed to 1.765-GHz microwaves in the uterus.