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1	Ameliorative Effect of the Oral Administration of Chuquiraga spinosa in a Murine Model of Breast Cancer Induced with 7,12-Dimethylbenz[a]anthracene (DMBA) Arroyo-Acevedo, Jorge Luis, Herrera-Calderon, Oscar, Tinco-Jayo, Johnny Aldo, Rojas-Armas, Juan Pedro, Rauf, Abdur, Hañari-Quispe, Renán, Figueroa-Salvador, Linder, Fernández-Guzmán, Victor, Yuli-Posadas, Ricardo Ángel 01 May 2020 (has links) Objective: To determine the ameliorative effect of the ethanolic extract of Chuquiraga spinosa (ChS) on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced breast cancer in rats. Methods: 36 female Holztman rats were divided into 6 groups. I) The negative control group received physiological saline (PS). II) ChS-200 group received 200 mg/kg of ChS. III) DMBA group was induced with DMBA (20 mg/Kg) dissolved in PS and administrated orally for 15 weeks. IV) DMBA + ChS-50 group, V) DMBA + ChS-250 group, and VI) DMBA + ChS-500 group, which received the extract orally for 15 weeks after DMBA induction. All data were expressed as mean and standard deviation. One-way analysis of variance (ANOVA) followed by Dunnet test was carried out to compare the mean value of different groups Histopathological analysis was evaluated by using Image J software. Results: Hematology showed that the triglyceride level was significantly lowered (P< 0.01) and high-density lipoprotein (HDL) level was significantly increased (P <0.01) in groups III, IV and V. Also, ChS extract significantly lowered the C reactive protein (CRP) level (P <0.01) and malondialdehyde level (P<0.05). There was a significant decrease in the frequency of DMBA-induced micronucleated polychromatic erythrocyte (P<0.01). Conclusions: Chuquiraga spinosa showed an ameliorative effect on DMBA-induced breast cancer in rats as well as antioxidant, antitumor and antigenotoxic properties. / Revisión por pares Anticarcinogenic agent Antioxidant Breast tumor Phytochemical Preventive medicine Toxicity 7,12 dimethylbenz[a]anthracene Alanine aminotransferasea Alkaline phosphatase Alkaloid derivative
2	Selective Retention of β-Carbolines and 7,12-Dimethylbenz[<i>a</i>]anthracene in the Brain : Role of Neuromelanin and Cytochrome P450 for Toxicity Östergren, Anna January 2005 (has links) <p>The ß-carbolines norharman and harman structurally resemble the synthetic compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that is known for its ability to damage neuromelanin-containing dopaminergic neurons of the substantia nigra and thereby induce parkinsonism. MPTP is, however, not normally present in the environment whereas the ß-carbolines are present in cooked food and tobacco smoke. </p><p>In this thesis it was demonstrated that norharman and harman had affinity to melanin and were retained in neuromelanin-containing neurons of frogs up to 30 days post-injection (the longest survival time examined). It was also demonstrated that norharman induced neurodegeneration, activation of glia cells and motor impairment in mice. Furthermore, this compound induced ER stress and cell death in PC12 cells. An in vitro model of dopamine melanin-loaded PC12 cells was developed in order to study the effect of melanin on norharman-induced toxicity. In this model, melanin seemed to attenuate toxicity induced by low concentrations of norharman. After exposure to the highest concentration of norharman, melanin clusters were disaggregated and there was an increased expression of stress proteins and caspases-3, known to be involved in apoptosis.</p><p>The polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[<i>a</i>]anthracene was demonstrated to have a CYP1A1-dependent localization in endothelial cells in the choroid plexus, in the veins in the leptomeninges and in the cerebral veins of mice pre-treated with CYP1-inducers. </p><p>These results demonstrate that the distribution of environmental compounds could be influenced by the presence of neuromelanin and expression of CYP enzymes in the brain and that norharman may induce neurotoxic effects in vivo and in vitro.</p> Toxicology β-carboline neuromelanin norharman harman parkinsonism Parkinson's disease motoric impairment behaviour glia cells substantia nigra dopamine melanin PC12 cells ER stress grp78 hsp90 cytochrome P450 CYP1A1 CYP1B1 blood-brain interfaces 7,12-dimethylbenz[a]anthracene polycyclic aromatic hydrocarbon endothelial cell smooth muscle cell bioactivation Toxikologi Toxicology Toxikologi
3	Selective Retention of β-Carbolines and 7,12-Dimethylbenz[a]anthracene in the Brain : Role of Neuromelanin and Cytochrome P450 for Toxicity Östergren, Anna January 2005 (has links) The ß-carbolines norharman and harman structurally resemble the synthetic compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that is known for its ability to damage neuromelanin-containing dopaminergic neurons of the substantia nigra and thereby induce parkinsonism. MPTP is, however, not normally present in the environment whereas the ß-carbolines are present in cooked food and tobacco smoke. In this thesis it was demonstrated that norharman and harman had affinity to melanin and were retained in neuromelanin-containing neurons of frogs up to 30 days post-injection (the longest survival time examined). It was also demonstrated that norharman induced neurodegeneration, activation of glia cells and motor impairment in mice. Furthermore, this compound induced ER stress and cell death in PC12 cells. An in vitro model of dopamine melanin-loaded PC12 cells was developed in order to study the effect of melanin on norharman-induced toxicity. In this model, melanin seemed to attenuate toxicity induced by low concentrations of norharman. After exposure to the highest concentration of norharman, melanin clusters were disaggregated and there was an increased expression of stress proteins and caspases-3, known to be involved in apoptosis. The polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene was demonstrated to have a CYP1A1-dependent localization in endothelial cells in the choroid plexus, in the veins in the leptomeninges and in the cerebral veins of mice pre-treated with CYP1-inducers. These results demonstrate that the distribution of environmental compounds could be influenced by the presence of neuromelanin and expression of CYP enzymes in the brain and that norharman may induce neurotoxic effects in vivo and in vitro. Toxicology β-carboline neuromelanin norharman harman parkinsonism Parkinson's disease motoric impairment behaviour glia cells substantia nigra dopamine melanin PC12 cells ER stress grp78 hsp90 cytochrome P450 CYP1A1 CYP1B1 blood-brain interfaces 7,12-dimethylbenz[a]anthracene polycyclic aromatic hydrocarbon endothelial cell smooth muscle cell bioactivation Toxikologi Toxicology Toxikologi

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