Animals ; Benzo(a)pyrene/toxicity* ; Cytokines ; Dibutyl Phthalate/toxicity* ; Female ; Liver ; Male ; NF-kappa B ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To analyze the effect of benzopyrene on the decrease of dopaminergic neurons, and the increase and aggregation of α-synuclein, which are the pathological features of Parkinson's disease, and to explore its possible mechanisms. METHODS: Eight-month-old transgenic mice with human SNCA gene were randomly divided into a BaP-exposed group and a control group. BaP and solvent corn oil were injected intraperitoneally to BaP-exposed group and control group respectively, once a day for 60 days. The motor dysfunction of mice was tested by rotarod test. The effects of BaP on the decrease of dopaminergic neurons and increase and aggregation of α-synuclein were observed by immunohistochemistry and Western blot experiments respectively, and the expression of related mRNA was detected by quantitative real-time PCR (qRT-PCR). Twenty genes were tested in the study, mainly related to neurotransmitter transporter (2 genes), neurotransmitter receptor function (10 genes), cellular autophagy (5 genes), and α-synuclein aggregation and degradation (3 genes). RESULTS: After BaP exposure, the movement time of the mice in the rotarod test was significantly reduced (P<0.05). The substantia nigra dopami-nergic neurons in the mice were significantly reduced, which was 62% of the control group (P<0.05), and the expression of α-synuclein in the midbrain increased, which was 1.36 times that of the control group (P<0.05). After BaP exposure, mRNA expressions of 14 genes in the midbrain of the mice were significantly down-regulated (P<0.05). Alpha-synuclein degradation and cell autophagy (5 genes), neuron transporters (2 genes), and neurotransmitter receptor functions (5 genes) were involved. The expression of one gene, Synphilin-1, was significantly up-regulated (P<0.01), which was related to α-synuclein aggregation. CONCLUSION BaP exposure not only inhibited function of neurotransmitter receptor and dopamine transporter, but also interfered cell autophagy, thereby hindering the degradation of α-synuclein, which could lead to decrease of dopaminergic neurons in substantia nigra and increase and aggregation of α-synuclein in midbrain, as the significant pathology of Parkinson's disease. Therefore, BaP exposure may increase the risk of Parkinson's disease.
Animals ; Benzo(a)pyrene ; Brain ; Dopamine ; Dopaminergic Neurons ; Humans ; Mice ; alpha-Synuclein

Metabolomics methods were applied in the study of the toxicity of environmental pollutants. It has been shown that exposure to heavy metals such as mercury, arsenic, cadmium, chromium and lead could cause significant changes in energy, lipids, nucleic acids and amino acids in mammalian cells. After exposure to benzo(a)pyrene [B(a)P], the glands of Pinctada pumila could produce various changes, such as energy metabolic disorder, cell damage, signal transduction disorder, oxidative stress and osmotic disorder. Persistent organic compounds polychlorinated biphenyls (PCBs) could exert toxic effects on Zebrafish embryos through affecting amino acid metabolism, DNA and protein methylation and biosynthesis. After exposure to endocrine disruptors, such as nonylphenol, octylenediester phthalate and bisphenol propane, goldfish showed energy, lipid and nucleic acid metabolic disorders.
Animals ; Benzo(a)pyrene ; Environmental Pollutants ; Metabolomics ; Oxidative Stress

OBJECTIVE: To investigate effects of benzo(a)pyrene (BaP) on expressions of insulin-degrading enzyme (IDE) and neprilysin (NEP) which have the ability to degrade β-amyloid (Aβ) in neuroglia cells. METHODS: Primary mix-neuroglia cells were cultured from newborn SD rats. After exposure to BaP, Aβ_1-42 oligomer or Aβ_1-42 fiber individually or jointly for 24 h, the cell survival rate was measured by cell counting kit-8 (CCK-8). Afterwards, the primary mix-neuroglia cells were divided randomly into six groups: Control group, BaP group (2.00 μmol/L), Aβ_1-42 oligomer group (20.00 mg/L), BaP plus Aβ_1-42 oligomer group, Aβ_1-42 fiber group (20.00 mg/L) and BaP plus Aβ_1-42 fiber group, of which BaP was pretreated for 12 h followed by cotreatment with different aggregated Aβ_1-42. The expressions of IDE and NEP were measured by quantitative real-time polymerase chain reaction (qRT-PCR) for mRNA level and Western blotting for protein level. RESULTS: The cell survival rate showed no significant differences after treatment with BaP (≤20.00 μmol/L), Aβ_1-42 oligomer (20.00, 40.00 mg/L), Aβ_1-42 fiber (20.00, 40.00 mg/L) or cotreatment with BaP and Aβ_1-42 oligomer or BaP and Aβ_1-42 fiber. Compared with the control group, expressions of IDE and NEP in BaP-treated alone group had no obvious change; however, exposure to Aβ_1-42 oligomer alone significantly increased the mRNA and protein level of IDE (P<0.05), and the BaP pretreatment could significantly inhibit the up-regulated expressions of IDE by Aβ_1-42 oligomer (P<0.05); on the other hand, exposure either to Aβ_1-42 fiber alone or under the BaP pretreatment did not change the mRNA and protein level of IDE and NEP obviously. CONCLUSION On the premise of no significant change of cell survival rate, BaP pretreatment inhibited the up-regulated expressions of IDE in primary mixed neuroglia cells under cotreatment with Aβ oligomer, indicating that BaP may disturb degradation of Aβ oligomer and cause deposition of β-amyloid and further induce cognitive decline and acceleration of Alzheimer.
Amyloid beta-Peptides ; Animals ; Benzo(a)pyrene ; Blotting, Western ; Insulysin/metabolism* ; Neprilysin/metabolism* ; Neuroglia/metabolism* ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Rice bran is the outer layer of the rice grain, and contains high amounts of bioactive phytochemicals. Here, we investigated and compared chemopreventive properties of purple and white rice bran extracts. METHODS: Rice bran was extracted with dichloromethane and methanol. Chemical constituents in the extracts were analyzed by colorimetric assay and high performance liquid chromatography. The mutagenicity and antimutagenicity of the extracts were determined via the Salmonella mutation assay. The anticarcinogenic enzyme induction and antioxidant activities of the extracts were examined using Hepa1c1c7 cells and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, respectively. RESULTS: The methanol extracts of rice bran contained high amounts of phenolic acids, flavonoids, anthocyanins, and phytic acid, whereas large amounts of γ-oryzanol and vitamin E were presented in the dichloromethane extract. None of the extracts were mutagenic to Salmonella typhimurium. All rice bran extracts had strong antimutagenic effects against aflatoxin B1- and 2-amino-3,4-dimethylimidazo [4,5-f]quinoline-induced mutagenesis. The inhibitory effect against 2-aminofluorene-induced mutagenesis was found in the dichloromethane extract, while only the methanol extract of purple rice bran exhibited antimutagenic effects against benzo(a)pyrene. None of the extracts induced quinone reductase activity in Hepa1c1c7 cells. Additionally, the greatest antioxidant capacity was found in the methanol extract of purple rice bran. CONCLUSIONS: The methanol extract of purple rice bran containing high amount of phenolic acids, flavonoids, anthocyanins, and phytic acid showed the most effective antioxidant and antimutagenic activities by inhibiting mutagenic metabolizing enzymes and/or scavenging free radicals. These results demonstrate the nutritional and medical value of Thai rice for cancer prevention.
Aflatoxins ; Anthocyanins ; Antimutagenic Agents ; Asian Continental Ancestry Group* ; Benzo(a)pyrene ; Chromatography, Liquid ; Enzyme Induction ; Flavonoids ; Free Radicals ; Humans ; Methanol ; Methylene Chloride ; Mutagenesis ; NAD(P)H Dehydrogenase (Quinone) ; Phenol ; Phytic Acid ; Phytochemicals ; Salmonella ; Salmonella typhimurium ; Vitamin E ; Vitamins

OBJECTIVETo observe protective effects of Schisandra extract (SE) on embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene (Bap).

METHODSPregnant rat model was prepared using periodic screening cage method. Totally 50 female pregnant SD rats were divided into five groups by randomized block design according to the weight, i.e., the BaP model group, the low dose SE group, the middle dose SE group, the high dose SE group, the normal control group, 10 rats in each group. Rats in the BaP model group were administered with BaP at a daily dose of 2 mg/kg by gastrogavage. Rats in low, middle, and high dose SE groups were administered by gastrogavage with BaP (at a daily dose of 2 mg/kg) plus SE at a daily dose of 40, 200, and 1 000 mg/kg, respectively. Equal volume of olive oil was administered to rats in the normal control group by gastrogavage. All medication was performed for 8 successive days. Changes of rat body weight in each period were observed. The uterus embryonic total quality and ovary quality were measured, and organ index calculated. The number of corpus luteum, the number of embryo implantation, and the number of absorbed embryo were statistically calculated respectively. The implantation rate and the absorbed embryos rate were calculated. Serum levels of human chorionic gonadotrophin β (β-HCG) and progesterone (PROG) were detected by ELISA.

RESULTSCompared with the normal control group, the weight of 9-day pregnant rats, the number of embryo implantation, the uterus embryonic total index, ovary index, serum levels of β-HCG and PROG all decreased in the Bap model group with significant difference (P < 0.05, P < 0.01). Compared with the Bap model group, body weight, the uterus embryonic total index, and the PROG level increased in 3 dose SE groups (P < 0.05, P < 0.01). Ovary index and serum β-HCG increased in middle and high dose SE groups (P < 0.05, P < 0.01). The number of implantation obviously increased in the high dose SE groups (P < 0.01).

CONCLUSIONSE could reduce the embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene.

Animals ; Benzo(a)pyrene ; toxicity ; Chorionic Gonadotropin ; blood ; Embryo Implantation ; drug effects ; Female ; Ovary ; drug effects ; Plant Extracts ; pharmacology ; Pregnancy ; Progesterone ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproduction ; drug effects ; Schisandra ; chemistry ; Uterus ; drug effects

OBJECTIVEThrough comparative study on pulmonary function damage of coke oven workers exposed to coke oven emissions with the same group before and after five years, and further explore the relationship between the coke oven emissions and injury in pulmonary function of coke oven worker.

METHODSSelect a coking plant in Shanxi 165 coke oven workers (exposed group) and 52 auxiliary workers (control group) for the study, using a uniform questionnaire to collect workers' personal information. Fixed workplace air samples collected periodically. Air samples of benzo (a) pyrene concentrations was measured by high pressure liquid chromatograph. Pulmonary function of research object was measured by portable spirometer respectively in 2009 and 2013, and comparative analysis on it.

RESULTSThe concentration of B(a)P was no significant difference in the same area between 5 years in 2009-2013. Compared with 2009, 2013 control workers lung function index and the abnormal rate had no significant difference (P > 0.05). But FVC%, FEV1.0%, MVV%, VC% and FEF25% of exposed workers in 2013 was significantly lower than in 2009, FVC%, FEV1.0%, VC% and FEF25% pulmonary dysfunction rate in 2013 was also significantly higher than in 2009, difference was statistically significant (P < 0.05). Workers emerging pulmonary function abnormalities mainly distributed in furnace roof and side. furnace roof group FVC%, FEV1.0%, VC% additional abnormal number (rate) was significantly higher than furnace floor and the control group (P < 0.05), and furnace side groop was significantly higher than the control group, the difference was statistically significant (P < 0.05). Multivariate Logistic regression analysis showed that after 5 years FVC%, FEV1% and VC% of abnormal lung function emerging adjusted OR of furnace roof workers were 7.939, 5.966 and 4.956. For abnormal of FVC%, FEV1%, VC% and MVV%, the contacting coke seniority is a risk factor. There is a positive interaction between contacting coke seniority and furnace roof (P < 0.05).

CONCLUSIONCoke oven workers lung function damage associated with exposureing to coke oven emissions, coke oven emissions exposure level and exposure time are the main factors of coke oven workers in lung function damage, there is a positive interaction between the two factors.

Air Pollutants, Occupational ; adverse effects ; analysis ; Benzo(a)pyrene ; adverse effects ; analysis ; Cohort Studies ; Coke ; Humans ; Lung ; drug effects ; physiopathology ; Occupational Exposure ; adverse effects ; Respiratory Function Tests ; Risk Factors ; Surveys and Questionnaires

OBJECTIVE: To investigate the effect of benzo(α)pyrene on the ATPase activity and content of Ca²⁺ in the hippocampus of neonatal SD rats. METHODS: Sixty male and 60 female 4-days-old neonatal SD rats were randomly divided into 5 groups (n=24): a blank control group, a vehicle control group (peanut oil), 3 benzo(α)pyrene groups (0.02, 0.2 and 2 mg/kg, respectively). SD rats were given benzo(α)pyrene (dissolved in peanut oil) by gavage daily from postnatal day 4 (PND4) to PND20. The nerve reflex, the condition of neuro-muscle development and motion function were examined in the period of treatment. The colorimetric technique was used to detect the activity of Ca²⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in hippocampus after the treatment. The concentration of Ca²⁺ of synapse in the hippocampus of rats was detected by fluorescent labeling. RESULTS: The results from the behavior tests showed that duration of surface reflex latency in rats with medium dose of benzo(α)pyrene was longer compared with that in the control group in PND12. The duration of surface reflex latency in rats with high dose of benzo(α) pyrene is longer in PND 14 and PND 16 compared with that in the control group (P<0.05). Compared with the rats in the control group, the activities of Ca²⁺-Mg²⁺-ATPase and Ca²⁺-ATPase in hippocampus in rats with high dose benzo(α) pyrene were significantly decreased, and the degree in the decrease of Ca²⁺-ATPase activity was dose-dependent (P<0.05). The contents of Ca²⁺ in the hippocampus in rats with medium or high dose of benzo(α) pyrene were significantly increased compared with that in the control group (P<0.05), which showed a dose-dependent manner (P<0.05). CONCLUSION Benzo(α)pyrene exposure led to the decrease in ATPase activity as well as Ca²⁺ overload of the synapse in the hippocampal tissue, which in turn results in the nerve damage of newborn SD rats.
Animals ; Benzo(a)pyrene ; toxicity ; Ca(2+) Mg(2+)-ATPase ; metabolism ; Calcium ; metabolism ; Calcium-Transporting ATPases ; metabolism ; Female ; Hippocampus ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the protective effects and the potential mechanisms of vitamin E (VE) on benzo(a)pryene (B[a]P)-induced toxicity in the reproductive system of male rats. 
 METHODS: A total of 60 male Sprague Dawley (SD) rats, weighted 70-90 g, were randomly assigned to 6 groups: a control group, a vehicle group, a B[a]P group (5 mg/kg), a VE (10 mg/kg)+ B[a]P (5 mg/kg) group, a VE (50 mg/kg) + B[a]P (5 mg/kg) group and a VE (100 mg/kg)+B[a]P (5 mg/kg) group (n=10 per group). The rats were treated with B[a]P and/or VE once a day for 30 days via intragastric administration. The sperm quality and the levels of SOD, GSH-Px, 8-OHdG and MDA were detected, respectively. The testicular tissue morphology and DNA damage were observed by HE staining and comet assay.
 RESULTS: The sperm count, the rate of sperm deformation, the content of MDA and 8-OHdG were all significantly increased in single B[a]P-treated group in comparison to the control groups. The activities of SOD and GSH-Px were markedly decreased by B[a]P as compared with the control groups (P<0.05). The injury of testicular tissue in B[a]P-treated rats was remarkably improved after VE treatment. The levels of oxidative stress and DNA damage indicators in the B[a]P-treated group were all attenuated by VE. These protective effects of VE were in a dose-dependent manner (P<0.05).
 CONCLUSION Vitamin E can protect the male SD rats against the B[a]P-induced reproductive toxicity.
Animals ; Benzo(a)pyrene ; toxicity ; DNA Damage ; Male ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spermatozoa ; drug effects ; Testis ; drug effects ; pathology ; Vitamin E ; pharmacology

OBJECTIVEThe oxidation of benzo (a) pyrene mediated by 5-lipoxygenase (5-LOX) were investigated in HBE cells in order to provide further proof that lipoxygenase is the alternative pathway for the oxidation of xenobiotics.

METHODSEnzymic experiment: Soybean lipoxygenase (SLO), substrate (benzo[a] pyrene) and other component react in the enzymic system and the reaction product are detected by spectrophotometry. At the same time, in vitro detect of benzo (a) pyrene-DNA adducts with a UV spectrophotometer and HPLC. Cellular experiment: After HBE cells exposure to different poison (B[a]P 4, 8, 16, 32, 64, 128µmol/L, AA-861, naproxen or α- naphthoflavone 0.1, 1, 10 µmol/L) for 24 hours, the effect of benzo (a) -pyrene on cell survival rate were assessed by reductions of tetrazolium dye (MTT) and flow cytometry in cultured HBE cells, and the protein expressions of 5-lipoxygenase in the cells are tested by western-blot, and the DNA damages by the single cell gel electrophoresis. And then, the effect of the specific inhibitor of 5-lipoxygenase (AA-861) on 5-lipoxygenase protein expression and DNA damage in the cells are detected.

RESULTSSLO can catalyze the co-oxidation of benzo (a) pyrene to generate benzo (a) pyrene-7,8-epoxide in the presence of hydrogen peroxide. GTP can inhibit the reaction , the IC50 value is 0.46 mg/L, the model equation is Probit (P) = 0.8985+2.6824 Log (dose). SLO can catalyze the co-oxidation of benzo (a) pyrene to generate a new product, but fail to form DNA adducts in vitro. HBE cell viability decreased with the benzo (a) pyrene concentration increased , but AA-861 and naproxen can inhibit it. Flow cytometry and single cell gel electrophoresis experiments show, Benzo (a) pyrene can induce 5-lipoxygenase protein expression, but AA-861 cannot in HBE. Benzo (a) pyrene causes toxic action and DNA damage in HBE, which can significantly inhibit by AA-861, the difference is statistically significant (P < 0.05).

CONCLUSIONSThe co-oxidate of benzo (a) pyrene by 5-LOX turns into electrophiles that covalently bind to DNA and induce DNA damage, which can be significantly inhibited by AA-861.

Benzo(a)pyrene ; metabolism ; Cells, Cultured ; DNA Adducts ; metabolism ; DNA Damage ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Lipoxygenase ; pharmacology