RESUMO
The neurotoxicity of the inhaled anesthetic, sevoflurane, has been documented in a number of studies. In this study, we conducted experiments to investigate whether Hirsutanol A (HA), a sesquiterpene compound from the fungus, Chondrostereum sp., can provide protection from sevoflurane-induced neurological toxicity in aged rats, and analyzed the underlying mechanisms. The cognitive dysfunction of rats following sevoflurane exposure was evaluated by behavioral tests. The neuronal cell survival was determined by Nissl staining. In addition, human neuroblastoma H4 cells were exposed to sevoflurane to establish an in vitro model. Apoptotic marker expression in hippocampal tissue was determined by western blotting. Cell apoptosis in vitro was also examined by TUNEL assay and flow cytometry. The expression and translocation of Nrf2 were examined by both western blot and immunofluorescence staining. Our results show that HA significantly attenuated sevoflurane-induced cognitive impairment in aged rats. In addition, HA treatment decreased sevoflurane-induced neuronal apoptosis in the hippocampus and alleviated Aß accumulation. Our results also show that the neuroprotective effect of HA is associated with the activation of Nrf2 signaling. Human neuroblastoma H4 cells were used as a model to examine the protective activity of HA against sevoflurane-induced neurotoxicity. In addition, our results show that the inhibition of Nrf2 by a specific inhibitor or targeting siRNA significantly compromises the attenuating effect of HA on sevoflurane-induced cell apoptosis and Aß accumulation. Our results suggest that HA may function as a neuroprotective agent against sevoflurane-induced neurotoxicity.
Assuntos
Anestésicos Inalatórios/efeitos adversos , Disfunção Cognitiva/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Sevoflurano/efeitos adversos , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To study the expression of p16 and nm23 genes in salivary gland tumors and the relation of P16 and nm23 proteins with fumorigenesis of salivary gland tumors. METHODS: Expression of P16 and nm23 proteins was examined by SABC immunohistochemical method in 39 cases of paraffin blocks of normal salivary gland tissues and salivary gland tumors. RESULTS: P16 and nm23 protein positive staining were mainly found in the cytoplasm and cytoblast of all salivary gland tissues. Positive rate of P16 protein expression was 76.9% (10/13) and 40.9% (9/22) in benign and malignant salivary gland tumors, respectively. There was significant difference between P16 protein expression of benign and malignant tumors by chi 2 test (P < 0.05). mm23 protein positive staining was found in 84.6% (11/13) and 45.5% (10/22) of benign and malignant tumors respectively. The expression of nm23 protein in benign and malignant tumors was significantly different (P < 0.05). There was no correlation of the expression of P16 and nm23 in salivary gland tumors was found (P > 0.05). CONCLUSION: p16 and nm23 genes may play an important role in different sides in salivary gland tumorigenesis and the reduce of the expression of p16 and nm23 genes may contribute to the generation of malignant salivary gland tumors.
