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1.
Toxicol Mech Methods ; 29(6): 457-466, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31010378

RESUMO

Cognitive deficits are commonly reported by patients following treatment with chemotherapeutic agents. Anthracycline-containing chemotherapy regimens are associated with cognitive impairment and reductions in neuronal connectivity in cancer survivors, and doxorubicin (Dox) is a commonly used anthracycline. Although it has been reported that Dox distribution to the central nervous system (CNS) is limited, considerable Dox concentrations are observed in the brain with co-administration of certain medications. Additionally, pro-inflammatory cytokines, which are overproduced in cancer or in response to chemotherapy, can reduce the integrity of the blood-brain barrier (BBB). Therefore, the aim of this study was to evaluate the acute neurotoxic effects of Dox on hippocampal neurons. In this study, we utilized a hippocampal cell line (H19-7/IGF-IR) along with rodent hippocampal slices to evaluate the acute neurotoxic effects of Dox. Hippocampal slices were used to measure long-term potentiation (LTP), and expression of proteins was determined by immunoblotting. Cellular assays for mitochondrial complex activity and lipid peroxidation were also utilized. We observed reduction in LTP in hippocampal slices with Dox. In addition, lipid peroxidation was increased as measured by thiobarbituric acid reactive substances content indicating oxidative stress. Caspase-3 expression was increased indicating an increased propensity for cell death. Finally, the phosphorylation of signaling molecules which modulate LTP including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and Akt were increased. This data indicates that acute Dox exposure dose-dependently impairs synaptic processes associated with hippocampal neurotransmission, induces apoptosis, and increases lipid peroxidation leading to neurotoxicity.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Doxorrubicina/toxicidade , Hipocampo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Técnicas de Cultura de Células , Linhagem Celular , Relação Dose-Resposta a Droga , Complexo I de Transporte de Elétrons/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos , Ratos Sprague-Dawley
2.
J Environ Biol ; 32(5): 567-72, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22319870

RESUMO

Biological invasions are increasingly attracting the ecologists' attention. Invasive plants threaten the natural ecosystems not only by competing with the native plants, but also by altering the structure and function of soil microbial communities belowground. In this study, we studied the effects of the invasive plant Coreopsis grandiflora (C. grandiflora) on the functional diversity of soil microbial communities in Laoshan mountain in the province of Shandong, North of China. We sampled soil from plots that were invaded or not invaded by C. grandiflora. The functional diversity of microbial communities in the sampled soils was assessed by the Biolog procedure test. By the ANOVA analysis of average well color development (AWCD), Shannon index (H'), Shannon evenness (E), principle components analysis of the level physiological profiles (CLPP) and correlation analysis between the studied parameters, we found that the invasive species C. grandiflora enhanced the functional diversity of soil microbial communities where the habitat was invaded by the C. grandiflora. The study indicated thatthe successful invasive plants have profound effects on the function of soil microbial communities.


Assuntos
Coreopsis/fisiologia , Espécies Introduzidas , Microbiologia do Solo , Bactérias/classificação , China , Análise de Componente Principal
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