The Effect of the iNOS Inhibitor S-Methylisothiourea and Hyperbaric Oxygen Treatment on Radiation Colitis in Rats.

INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S-Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2 ml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10 mg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test for : tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1ß, transforming growth factor-ß (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-α, IL-1ß, IL-10 and TGF-ß levels were reduced by SMT, HOT and HOT+SMT applications (p < 0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (p < 0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately.

Antitumor effects of Origanum acutidens extracts on human breast cancer.

PURPOSE: There has been a long-standing interest in the identification of medicinal plants and derived natural products for developing anticancer agents. This work aimed at investigating the antiprolipherative properties of Origanum acutidens (OA) on breast cancer. METHODS: OA water extracts were studied for cytotoxicity against the breast cancer cell lines MCF-7, MDA-MB-468 and MDA-MB-231. In vitro apoptosis studies of these cancer cell lines were performed by annexin V staining in flow cytometry analyses. Immunohistochemistry studies for Ki-67 and caspase-7 of tumor tissue sections of dimethylbenzanthracene (DMBA) -induced mammary cancer in rats were also performed. TUNEL assay was used to detect apoptotic cells of tumor tissue. In vivo anticancer activity testing was carried out by inhibiting the growth of DMBA-induced mammary cancer in rats. RESULTS: OA showed cytotoxicity on all 3 cancer cell lines. Annexin-positive cells level in OA-treated cell lines were significantly higher compared with untreated control cells (p=0.002). The expressions of caspase-7 protein and TUNEL-positive cells were much higher for the rats treated by OA, compared with the untreated control group (p<0.05). The expressions of the Ki-67 decreased in the treated groups compared with the control group (p<0.05). In vivo studies showed that the mean tumor volume inhibition ratio in OA-treated group was 41 % compared with the untreated rats (p<0.05). CONCLUSION: These results indicate that OA has antitumor activity against breast cancer cell lines.