study on the possible protective effect of some antioxidants in cigarette smoke-induced oxidative stress in the rat

The design of the present work was set to detect how smoking challenges the antioxidant defense system and to evaluate the possible protective effects of three antioxidants namely, vitamin C, vitamin E and sodium selenite, given either singly or in combination, on oxidative stress induced by cigarette smoke [CS]. The study also examined the effect of CS exposure on endothelin-1 [ET-1] production and the influence of the probed antioxidants. Sixty rats were used in the current study, they were divided into 6 groups, each of ten animals. Group I served as normal controls. Rats in group II were exposed to cigarette smoke for 15 minutes, twice daily, 6 days/week for 8 weeks. Rats in group III, IV and V received vitamin C [75 mg/kg.b.wt], vitamin E [150 mg/kg.b.wt] and sodium selenite [100 micro g/kg b.wt], orally, half an hour prior to cigarette smoke exposure. Group VI received a combination of vitamin C 25 mg/kg b.wt, vitamin E 50 mg/kg b.wt and sodium selenite 33.3 micro g/kg b.wt.], orally, half an hour prior to CS exposure. At the end of the experiment, plasma samples were withdrawn for plasma ET-1 estimation. Liver homogenates were prepared for determination of malondialdhyde [MDA], glutathione peroxidase [GPx], superoxide dismutase [SOD] and reduced glutathione [GSH] levels by biochemical methods. Cigarette smoke exposure was associated with increased oxidative stress as manifested by a significant increase in MDA level and a significant decrease in GSH concentration, GPx and SOD activities. Administration of vitamin C, vitamin E, Na selenite or the antioxidant combination produced a significant decrease in oxidative stress, in variable degrees, as manifested by a significant decrease in MDA level and significant increase in GSH concentration, GPx and SOD activities. The previous advantageous effects were more pronounced with the use of the antioxidant combination. This may be explained by the interaction between these antioxidants, working together in a network, recycling each other and thus creating an effective antioxidant defense system. Data also revealed that cigarette smoke exposure for 8 weeks, did not significantly affect plasma ET-1 level. A significant rise in plasma ET-1 level was only found in the selenium and combined antioxidant-supplemented groups. Supplementation with an antioxidant combination offers protection to macromolecules better than that offered by a single antioxidant, in CS-induced oxidative stress

Effect of tamoxifen on estrogen receptor negative breast cancer cells

This study was undertaken to investigate the mechanism[s] underlying the use of tamoxifen [TAM], a selective estrogen receptor modulator [SERM], in estrogen receptor [ER] negative breast cancer and to assess the role of TAM on lymphokine activated killer [LAK] cells reactive to autologous breast cancer cells. Twenty female breast cancer patients attending the outpatient clinic of the Medical Research Institute were enrolled in this study. All patients had modified radical mastectomy. Pieces of fresh breast tumor cells and their in vitro generated autologous LAK were treated with different doses of TAM prior to or during the cytotoxicity assay. Estrogen receptors were measured using the enzyme immunoassay kit. Treatment of effector cells with TAM did not affect their lytic function against their autologous breast cancer cells, irrespective of their ER state. However, TAM pretreatment of ER positive breast cancer cells resulted in their significant lysis by their autologous LAK cells. The degree of enhancement was directly proportional to the dose of TAM. On the other hand, pretreatment of ER negative breast cancer cells with TAM did not affect their lytic response to autologous LAK cells. An enhanced cytolytic effect was only observed for ER negative breast cancer cells when TAM was directly added to the cytotoxicity assay, indicating an indirect mode of action through the release of mediators. The data provide an evidence of a dual mechanism of action of TAM, one direct, which is evident against ER positive cancer cells while the other is indirect through the release of mediators. This might explain the usefulness of selective estrogen receptor modulators in ER negative breast cancer patients