ABSTRACT
Organoselenium compounds are bioactive substances with extensive physiological activities .As a representa-tive compound ,ebselen could be used as mimics of glutathione peroxidase ,and in the treatment of many diseases ,such as car-diovascular and cerebrovascular diseases ,inflammation and noise-induced hearing loss .the research progress in physiological activities and synthetic methods of ebselen were reviewed in this paper .
ABSTRACT
We evaluated the potential neuroprotective effect of 1-100 µM of four organoselenium compounds: diphenyl diselenide, 3’3-ditri-fluoromethyldiphenyl diselenide, p-methoxy-diphenyl diselenide, and p-chloro-diphenyl diselenide, against methylmercury-induced mitochondrial dysfunction and oxidative stress in mitochondrial-enriched fractions from adult Swiss mouse brain. Methylmercury (10-100 µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, which occurred in parallel with increased glutathione oxidation, hydroperoxide formation (xylenol orange assay) and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with diphenyl diselenide (100 µM) completely prevented the disruption of mitochondrial activity as well as the increase in TBARS levels caused by methylmercury. The compound 3’3-ditrifluoromethyldiphenyl diselenide provided a partial but significant protection against methylmercury-induced mitochondrial dysfunction (45.4 ± 5.8 percent inhibition of the methylmercury effect). Diphenyl diselenide showed a higher thiol peroxidase activity compared to the other three compounds. Catalase blocked methylmercury-induced TBARS, pointing to hydrogen peroxide as a vector during methylmercury toxicity in this model. This result also suggests that thiol peroxidase activity of organoselenium compounds accounts for their protective actions against methylmercury-induced oxidative stress. Our results show that diphenyl diselenide and potentially other organoselenium compounds may represent important molecules in the search for an improved therapy against the deleterious effects of methylmercury as well as other mercury compounds.
Subject(s)
Animals , Male , Mice , Brain/drug effects , Membrane Potential, Mitochondrial/drug effects , Mercury Poisoning, Nervous System/prevention & control , Methylmercury Compounds/toxicity , Mitochondria/drug effects , Neuroprotective Agents/pharmacology , Organoselenium Compounds/pharmacology , Oxidative Stress/drug effects , Analysis of Variance , Benzene Derivatives/pharmacology , Cell Fractionation , Models, Animal , Neuroprotective Agents/classification , Organoselenium Compounds/chemistryABSTRACT
DMBA (7,12-dimethylbenz[a]anthracene) is known to generate DNA-reactive species during their metabolism, which may enhance oxidative stress in cells. Since selenium is known as a non-enzymic antioxidant, health problems induced by many environmental pollutants, have stimulated the evaluation of relative antioxidant potential of selenium and synthetic organoselenium compounds. Therefore, we aimed to evaluate chemopreventive potential of synthetic organoselenium compounds by monitoring level of liver nitric oxide. In this study, adult female Wistar rats were treated with DMBA and the novel organoselenium compounds (Se I) and (Se II) in the determined doses. DMBA-induced in rats, the effects of organoselenium compounds on nitric oxide levels in rat liver was studied. In this study, it has been observed a statistically significant increase in (Nitric Oxide) levels for the liver of rat exposed to DMBA (p<0.05). However with administration of Se I and Se II there was a statistically significant decrease in NO levels (p<0.05). The ability of the organoselenium compounds to prevent oxidative damage induced by DMBA in rat livers was rationalized. Protection against nitric oxide measured in Se I and Se II treated groups were provided by synthesized organoselenium compounds. Se I and Se II both provided chemoprevention against DMBA-induced oxidative stress in rat liver.
ABSTRACT
Objective: To detect the Immune regulating activity of ethaselen-1(Eb1),a novel organoselenium compound,in C57/BL mice transplanted with Lewis lung cancer(LLC).Methods: The LLC transplanted C57/BL mice models were established,and the mice was randomly divided into four groups,including high dose Eb1 group(25.0 mg/kg),low dose Eb1 group(12.5 mg/kg),positive control group(levamisole,LMS,2.0 mg/kg) and negative control group(solvent).Intraperitoneal injections(ip.) of the four pharmaceuticals were performed once a day through the abdominal wall separately,from the second to the eighth day after cancer was transplanted.On the eleventh day,six mice of each group were killed and relative weight of spleen,transforming activity of spleen lymphocytes,NK cell activity,LAK cell activity and percentage of CD_4~+CD_8~+T lymphocyte were detect.Results: Compared with the control group,high dose Eb1 could obviously increase the relative weight of spleen(150.59% and 122.55%),transforming activity of spleen lymphocytes(162.25% and 561.98%),NK cell activity(78.60% and 219.42%) and percentage of CD_4~-/CD_8~+ T lymphocyte(104.72% and 105.87%) in normal mice and LLC mice.Compared with the control group,high dose Eb1 could also increase LAK cell activity of LLC mice by 195.11%.Conclusion: The novel organoselenium compound Eb1 has immune regulating activity in vivo.
ABSTRACT
Objective: To detect the antitumor activity of Shuang-Xi-Zuo-Wan-1(Eb), a novel organoselenium compound, in C57/BL mice transplanted with Lewis lung cancer(LLC). Methods: The LLC transplanted C57/BL mice model was established,and the mice were randomly divided into four groups, including high dose Eb group (25.0 mg/kg),low dose Eb group (12.5 mg/kg), positive control group (DDP,2.0 mg/kg) and negative control group(solvent).Each group had twelve mice. Intraperitoneal injections (ip.) of four pharmaceuticals were performed once a day through the abdominal wall separately, from the second to the eighth days after cancer was transplanted. On the eleventh day,six mice of each group were killed and the influences of Eb on growth speed ,size, weight, invasion, inhibitory rate, proliferation index and apoptosis rate of LLC were observed and calculated.The remaining mice were fed till all of them died naturely and the average survival time of each group was calculated. Results:Eb could inhibit the growth and infiltration of LLC(the cancer inhibitory rate of high does Eb was 80.31%) obviously and prolong the average survival time of these with mice cancer. After being given Eb,the nuclear of the cancer cell concentrated and the fission phase cells reduced.In addition,the number of apoptosis cancer cells increased.Conclusion:The novel organoselenium compound Eb has antitumo activity in vivo .It can inhibit the growth and infiltration of LLC in mice, and induce the apoptosis of cancer cells.