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Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and beta-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitration of proteins in cells above basal levels as determined by Western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31-10 microM) of lycopene and beta-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 microM). The protective effects of lycopene and beta-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo.  相似文献   
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Concentrations of lead, cadmium, and other metals in the liver and kidneys of cattle near a lead-zinc mine in Kabwe (Zambia), which is ranked among the 10 worst polluted places on earth, were compared with other Zambian towns. Metal concentrations were measured in the liver and kidneys of 51 cattle from Kabwe and other Zambian towns. The maximum metal concentrations, expressed in mg/kg and dry weight, in the liver or kidneys were 398.4 (Cu), 252.6 (Zn), 77.81 (Cr), 19.37 (Cd), 7.57 (Ni), 1.8 (Pb), 1.04 (Co), 0.112 (Hg), and 0.05 (As). Concentrations of Pb and Cd in Kabwe cattle were higher than levels in other Zambian towns. The mean concentration of Cd exceeded benchmark values in offal destined for human consumption. Levels of Ni and Cr may also pose public health concerns. Concentrations of Pb and Cr, Pb and Cu, Cd and Zn, Cd and Hg, Zn and Cu, Cu and Co, as well as Co and Ni were positively correlated. The present study also highlighted the dangers of exposure of animals and humans to a mixture of toxic metals.  相似文献   
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The present study was designed to describe the pharmacokinetics and fecal excretion of fenbendazole (FBZ) and fenbendazole sulphoxide (FBZSO) and their metabolites in horses, to investigate the effects which concurrent feeding has on the absorption and pharmacokinetics of FBZ, and to determine the effect of coadministration of the metabolic inhibitor piperonyl-butoxide on the in vivo pharmacokinetics and in vitro liver microsomal metabolism of sulfide and sulfoxide benzimidazoles. The effect of piperonyl-butoxide on the enantiomeric genesis of the sulfoxide moiety was also investigated. Following administration of FBZSO and FBZ, the fenbendazole sulphone metabolite predominated in plasma, and the C(max) and area under the plasma curve (AUC) values for each moiety were larger (P < 0.001) following FBZSO than FBZ. In feces the administered parent molecule predominated. The combined AUC for active benzimidazole moieties following oral administration of FBZ (10 mg/kg) in horses was almost 4 times as high in unfed horses (2.19 microg x h/ml) than in fed horses (0.59 microg x h/ml), and coadministration of piperonyl-butoxide significantly increased the AUC and C(max) of active moieties following intravenous administration of FBZSO and oral administration of FBZ. When FBZSO was administered i.v. as a racemate, the first enantiomer of oxfendazole (FBZSO-1) predominated in plasma, however, following coadministration with piperonyl-butoxide, the second enantiomer of oxfendazole (FBZSO-2) predominated for 10 h. Piperonyl-butoxide significantly reduced the oxidative metabolism of FBZSO and FBZ in equine liver microsomes and altered the ratio of enantiomers FBZSO-1/FBZSO-2 from >4:1 to 1:1. It is concluded that in horses efficacy of FBZSO and FBZ could be improved by administration to unfed animals and coadministration with piperonyl-butoxide.  相似文献   
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The Copperbelt region, upstream of the Kafue River, including Lake Itezhi-tezhi (ITT), in Zambia has extensive copper (Cu) mines. In our field study, geographic information system analysis in lake sediment indicated that the northern part of the lake, i.e., the Copperbelt region, could be the source of Cu pollution. Concentrations of Cu in stomach contents between fish species were not significantly different. However, Oreochromis spp. liver showed significantly greater Cu concentrations than those in other fish species. Log liver [Cu], standard length, and nitrogen stable isotope ratio were positively correlated only in Oreochromis spp. In the laboratory study, O. niloticus and O. latipes were exposed to Cu for 4 days, and recovery phases ≤28 days were examined. O. niloticus showed significantly greater concentrations of Cu compared with O. latipes at all sampling points. Significantly greater concentrations of Hg in Schilbe intermedius liver than for other fish species were observed, whereas O. macrochir showed significantly greater concentrations of cadmium. In conclusion, the northern part of the lake could be the source of Cu pollution in Lake ITT. Diet may not be the reason for high Cu accumulation in Oreochromis spp. Results from both field and laboratory studies imply that Oreochromis spp. contain high concentrations of Cu under normal physiological conditions.  相似文献   
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We measured the level of heavy metal accumulation in lake sediments, herbivorous (Oreochromis niloticus) and carnivorous (Serranochromis thumbergi) fish, and crayfish (Cherax quadricarinatus) from Lake Itezhi-tezhi (ITT) and Lake Kariba. We used atomic absorption spectrophotometry to quantify the levels of seven heavy metals (Cr, Co, Cu, Zn, Cd, Pb, and Ni). The sediment and the herbivorous fish O. niloticus accumulated a very high concentration of Cu in Lake ITT, most likely due to the discharge of Cu waste from a mining area 450 km upstream. The aquatic species we sampled in Lake Kariba had higher concentrations of Cr, Ni, and Pb relative to those in Lake ITT. This is most likely due to anthropogenic activities, such as the use of leaded petrol and antifouling agents in marine paints. Interestingly, we observed a negative correlation between the coefficient of condition (K) and Ni concentration in the crayfish hepatopancreas. Both O. niloticus and the crayfish had much higher biota-sediment accumulation factors (BSAF) for Cu, Zn, and Cd relative to Cr, Co, Pb, and Ni. The rank of BSAF values for O. niloticus (Cu > Cd > Zn) and C. quadricarinatus (Zn > Cd > Cu) differed from the expected ranks based on the general order of affinity of metals (Cd >> Zn > Cu).  相似文献   
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