Diphenyl diselenide supplementation delays the development of N-nitroso-N-methylurea-induced mammary tumors

Archive für Toxikologie (Impact Factor: 5.98). 09/2008; 82(9):655-663. DOI: 10.1007/s00204-007-0271-9


The effect of dietary diphenyl diselenide (1ppm) on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis was examined in female Wistar rats. Beginning at 5weeks of age, the animals
were fed with either control or diphenyl-diselenide-supplied diets until the end of the study (210days). At 50days of age,
mammary tumor was induced by the administration of three doses of NMU (50mg/kg body wt, intraperitoneally) once a week for
3weeks. In experimental trials, latency to tumor onset was extended in rats fed with diet supplemented with diphenyl diselenide
(P<0.05). The incidence and frequency of tumors were significantly small in animals supplemented with diphenyl diselenide.
However, the multiplicity of tumors was not altered by dietary diphenyl diselenide. Diphenyl diselenide supplementation also
restored superoxide dismutase (SOD) activity and vitamin C levels altered in the NMU group (P<0.05). Our results suggest that diphenyl diselenide can be considered a chemopreventive agent, even when supplemented at
a relatively low concentration.

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Available from: Cristina W Nogueira, May 30, 2014
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    • "Control and MTZ groups were supplied with a standard diet, whereas Se and Se + MTZ groups received a diet supplemented with diphenyl diselenide at 5 ppm, which provided approximately 5 μg selenium/g of diet/per day (≈ 0.3 mg/kg body weight). The choice of this concentration was based in previous studies from our research group indicating that chronic dietary diphenyl diselenide did not cause toxic effects in rats [40] [42] [43]. The food was prepared in an industrial mixer to allow the uniformity of the mixture, and the diphenyl diselenide was dissolved in soybean oil. "
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    ABSTRACT: Hypothyroidism has been associated to psychiatric disorders development and tissue oxidative damage. In this study, we evaluated the effect of diphenyl diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein (NP-SH) thiols levels were analyzed in cerebral cortex, hippocampus and striatum structures. Monoamino oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20mg/100ml in the drinking water for 30days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5ppm of diphenyl diselenide, and then they were evaluated monthly in open-field and FST tests during 3months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by diphenyl diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. MTZ group had an increase in TBARS and ROS levels that were restored by diphenyl diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or diphenyl diselenide supplementation. Diphenyl diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by methimazole triggers a depressive-like behavior in female rats and that dietary diphenyl diselenide was able in reducing this effect.
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    • "Se is bioaccumulated in the trophic chain, which may cause insidious toxic effects in fish populations, including reproductive problems and teratogenicity (Lemly 2002; Hamilton 2004). Diphenyl diselenide, a simple synthetic organoselenium compound, has been considered a potential pharmacological agent in several experimental models when used at low doses (Barbosa et al. 2008; de Vargas et al. 2008). This element exhibits antioxidant, neuroprotective, anti-nociceptive, and anti-inflammatory properties in different experimental models (Nogueira et al. 2003; Barbosa et al. 2008; de Freitas and Rocha 2011). "
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    ABSTRACT: Several diets employed in aquaculture are enriched with selenium (Se), as it is a fundamental element to aquatic vertebrates. Diphenyl diselenide [(PhSe)2], which is a synthetic organoselenium compound, has been considered a potential antioxidant agent in different experimental models. Thus, the aim of this study was to evaluate the effects of dietary diphenyl diselenide at concentrations of 1.5, 3.0, and 5.0 mg/kg for 60 days and to determine its optimal supplemental level for carp, Cyprinus carpio. Neither growth retardation nor hepatoxicity was induced by the inclusion of diphenyl diselenide at concentrations ranging from 1.5 to 5.0 mg/kg. In addition, the inclusion of 3.0 mg/kg of diphenyl diselenide stimulated the weight and length of the carp. The supplementation with 1.5 and 3.0 mg/kg of diphenyl diselenide did not produce oxidative damage in the tissues, verified by peroxidation lipid and protein carbonyl assays. However, at 5.0 mg/kg, it caused an increase of the lipid peroxidation in the liver, brain, and muscle, and inhibited the cerebral acetylcholinesterase activity. An increase of the hepatic superoxide dismutase activity and non-protein thiols content in all tissues and ascorbic acid in the liver, gills, and brain was verified in carp fed with the diet containing 3.0 mg/kg of diphenyl diselenide. This diet had advantageous effects for the fish used in experiments. Therefore, this compound could be considered a beneficial dietary supplement for carp nutrition.
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    • "About 70% of breast cancers are estrogen-dependent; however, its etiology remains obscure and primary prevention strategies are yet not available. Advances in therapy are limited and alternatives need to be developed for breast cancer control (3, 4). "
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    ABSTRACT: N-nitroso-N-methylurea (NMU) induces breast cancer in rodents, particularly in rats. This model of breast cancer is very similar to human breast cancer. As a continuation of our recent work, we investigated the expressions of cyclin D1 and p21 in NMU-induced breast cancer of Wistar Albino rats. In this experimental study, mammary carcinoma was induced in female Wistar Albino rats by a new protocol which included the intraperitoneal injection of NMU (50 mg/kg) at 50, 65, and 80 days of the animal's age. The animals were weighed weekly and palpated in order to record the numbers, location, and size of tumors. Subsequently tumor incidence (TI), latency period (LP), and tumor multiplicity (TM) were reported. About four weeks after the tumor size reached 1.5 cm3, rats were sacrificed. Cyclin D1 and p21 expressions in tumors and normal mammary glands from normal rats were measured by reverse-transcription polymerase chain reaction (RT- PCR) and Western blot analysis. Statistical analysis of the data was performed using SPSS software version 16.0. The efficiency of tumor induction was 65%, LP was 150 days, and a TM of 1.43 ± 0.53 per rat was noted. RT-PCR and Western blot data indicated significant (p<0.05) induction of both cyclin D1 and p21 expressions in rat mammary tumors compared with normal tissue from the control group. These results indicate an efficient mammary tumor induction protocol for this type of rat, which is accompanied by an increase in cyclin D1 and p21 expressions.
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