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Cadmium(Cd) and chlorpyrifos (CPF) are widespread harmful environmentalpollutants with neurotoxicity to mammals. Although the exposure toCd and CPF at the same time may pose a significant risk to human health,the subchronic combined neurotoxicity of these two chemicals at lowlevels in the brain is poorly understood. In this study, we treatedrats with three doses (low, middle, and high) of Cd, CPF, or theirmixture for 90 days. No obvious symptom was observed in the treatedanimals except those treated with high-dose CPF. Histological resultsshowed that middle and high doses of the chemicals caused neuronalcell damage in brains. GC–MS-based metabonomics analysis revealedthat energy and amino acid metabolism were disturbed in the brainsof rats exposed to the two chemicals and their combinations even atlow doses. We further identified the unique brain metabolite biomarkersfor rats treated with Cd, CPF, or both. Two amino acids, tyrosineand l-leucine, were identified as the biomarkers for Cd andCPF treatment, respectively. In addition, a set of five unique biomarkers(1,2-propanediol-1-phosphate, d-gluconic acid, 9H-purine, serine, and 2-ketoisovaleric acid) was identified for themixtures of Cd and CPF. Therefore, the metabolomics analysis is moresensitive than regular clinical observation and pathological examinationfor detecting the neurotoxicity of the individual and combined Cdand CPF at low levels. Overall, these results identified the uniquebiomarkers for Cd and CPF exposure, which provide new insights intothe mechanism of their joint toxicity. [ABSTRACT FROM AUTHOR]

During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What's more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2. [ABSTRACT FROM AUTHOR]

Pesticides and heavy metals can be easily biomagnified in food chains and bioaccumulated in individuals, thus pose significant threat to human health. However, their joint toxicity for long-term exposure at low dose has not been thoroughly investigated. In the present study, we investigated the oxidative damages in brain of rats exposed subchronically to organophosphorus pesticide chlorpyrifos (CPF) and heavy metal cadmium (Cd), and their mixtures at the environmentally relevant doses. Rats were given different doses of CPF and Cd by oral gavage for three months. After treatment, brain tissues were subjected for biochemical analysis. Mitochondrial damage and reactive oxidative species were also measured in neuroblastoma SH-SY5Y cells treated with CPF, Cd and their mixtures. The results showed that CPF and Cd generated protein and lipid peroxidation, disturbed the total antioxidant capability, and altered mitochondria ultrastructure in the brain. Lipids and proteins were sensitive to the oxidative damage induced by CPF and Cd. CPF and Cd decreased mitochondrial potential and induced reactive oxygen species in SH-SY5Y cells. However, the mixture did not display higher toxicity than the sum of that of the individual treatments. Thus, CPF and Cd could have a potential antagonistic interaction on the induction of oxidative stress. [ABSTRACT FROM AUTHOR]