Fish oil omega-3 fatty acids reduce the severity of radiation-induced oxidative stress in the rat brain.

PURPOSE: To evaluate the modulator role of fish oil (FO) on some biochemical changes in the brain of gamma-irradiated rats (RAD). MATERIAL AND METHODS: Male albino rats Sprague Dawley were divided into four groups (n = 10). (i) CONTROL: received vehicle via gavages during 28 days; (ii) FO: received fish oil (400 mg/kg/day) via gavages during 28 days; (iii) RAD: received vehicle for 7 days before whole body gamma-irradiation with 8 Gy given in four fractions each 7 days apart and continued during the irradiation period; and (iv) FO+ RAD: received FO for 7 days before exposure to the first dose of irradiation and FO treatment was continued during the irradiation period. Animals were sacrificed 24 hours post the last irradiation dose. RESULTS: A significant increase of malondialdehyde (MDA) and protein carbonyl (CO) content associated with a significant decrease of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content were recorded in the brain of irradiated rats. Oxidative stress was accompanied by a significant decrease of eicosapentaenoic (EPA) and docosahexaenoic (DHA) levels. Aspartic (Asp) and glutamic (Glu) acid levels were increased. Serotonin level showed a decrease associated with enhanced monoamine oxidase (MAO) activity and increased 5-hydroxyindolacetic acid (5-HIAA) level. FO treatment reduced the severity of radiation-induced oxidative stress, alteration of Asp and Glu levels and serotonin metabolism concomitant with increased EPA and DHA levels. CONCLUSION: FO attenuates the severity of radiation-induced biochemical disorders in the brain by counteracting the radiation-induced decrease of EPA and DHA. Further studies are needed concerning the long-term implications of our findings.

A new class of antimetabolites: pyridine thioglycosides as potential anticancer agents.

The present study was designed for highlighting and focusing on the cytotoxic activity of a new class of antimetabolites both on human cell lines, namely liver carcinoma cell line (Hepg2), lung carcinoma cell line (H460), breast carcinoma cell line (MCF7), brain carcinoma cell line (U251), and animal cell line EAC (Ehrlich ascites carcinoma cells). The results revealed that some of these modified deazapyrimidine thioglycosides have significant cytotoxic activity against EAC cells with growth inhibition percentage ranged between 80% to 90%. The possible inhibitory mechanism of the pyridine thioglycosides was explored by studying the cell cycle perturbation of thioglycosides against human cell lines (in vitro) as well as the most suitable time for maximum compound cytotoxic activity after 6, 18, and 24 h of incubation. To confirm the cytotoxic activity of these compounds, they have been tested for their apoptotic and antiproliferative activity in vivo against solid Ehrlich tumours using five groups of Swiss albino mice for 37 days from inoculation and three treatments, 250, 500 and 1000 microg/kg body weight. There was significant reduction in Ehrlich tumour size in case of the 500 and 1000 microg/kg body weight group but mild significant tumour reduction in the 250 microg/kg body weight group. Histograms of DNA per cell for each treatment group indicated that there was a dose-dependent increase in the preG1 phase with a corresponding complete arrest of cells from entering the G2/M phase compared to the untreated EAC group. In conclusion, pyridine thioglycosides have proven good cytotoxic effects against EAC cells and also significant cytotoxic activity against the four tested human cell lines. Flow cytometric DNA ploidy analysis of pyridine thioglcyosides against the Hepg2 and U251 cell lines revealed that the postulated mechanism of action of pyridine thioglcyosides is cell cycle arrest in the S phase. This is similar to antimetabolites and cell cycle arrest in the G2/M phase (M phase) in the same way as microtubule inhibitors like pyridine thioglycosides are cell-cycle-specific in the S phase and the M phase (in case of human cell lines) and have apoptotic effects (in case of animal cell line).