RESUMO
Sevoflurane, the most widely used anesthetic in clinical practice, has been shown to induce apoptosis, inhibit neurogenesis, and cause learning and memory impairment in young mice. However, the underlying mechanism is still unknown. In this study, wild-type and the FAS- or FAS ligand (FASL)-knockout mice (age 7 days) were exposed to sevoflurane or pure oxygen. Western blotting was used to examine the expression of FAS protein. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and bromodeoxyuridine (BrdU) staining were employed to quantify the apoptotic cells and newborn cells in the hippocampus and Morris water maze (MWM) in order to evaluate learning and memory status. Sevoflurane significantly increased the expression of FAS protein in wild-type mice. Compared to FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane-treated wild-type mice exhibited more TUNEL-positive hippocampal cells and less BrdU-positive hippocampal cells. The MWM showed that compared with FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane treatment of wild-type mice significantly prolonged the escape latency and reduced platform crossing times. These data suggest that sevoflurane induces neurotoxicity in young mice through FAS-FASL signaling.
Assuntos
Proteína Ligante Fas/genética , Éteres Metílicos/efeitos adversos , Síndromes Neurotóxicas/genética , Receptor fas/genética , Anestésicos/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Proteína Ligante Fas/biossíntese , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Knockout , Neurogênese/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Sevoflurano , Receptor fas/biossínteseRESUMO
The dried roots of the plant Acanthopanax senticosus (AS) are used in traditional Oriental medicine and reportedly possess anti-inflammatory properties in vitro. However, whether AS has the same anti-inflammatory effect in vivo and the underlying mechanisms of this action remain unknown. In this study, we pretreated a mouse model of lipopolysaccharide-induced acute lung injury with AS and found that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and neutrophils in bronchoalveolar lavage fluid were reduced and that inflammation in lung tissues was attenuated. To determine the mechanisms of these actions, we next assessed the effects of AS on the activation of the nuclear factor (NF)-kB pathway. We found that AS decreased the level of NF-kB and the DNA-binding activity of NF-kB. In summary, we found that AS attenuated the levels of TNF-α and IL-6 in the lung tissue of a mouse model of acute lung injury by inhibiting the NF-kB pathway.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Inflamação/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Eleutherococcus/química , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , NF-kappa B/antagonistas & inibidores , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Previous studies have found that children with multiple exposures to anesthesia at an early age are at increased risk of learning and memory impairment. Sevoflurane is the most commonly used inhalational anesthetic for general anesthesia in children. Multiple exposures to sevoflurane have been shown to induce neuroinflammation, inhibit neurogenesis, and cause subsequent learning and memory impairments in fetal mice. Histone-tail acetylation has been implicated in memory formation. In this study, we employed suberanilohydroxamic acid (SAHA), an inhibitor of histone deacetylases, to treat sevoflurane-induced learning and memory impairments. Six-day-old C57BL/6 mice were exposed to sevoflurane for 2 h daily for 3 days. Morris water maze test performed to evaluate learning and memory impairments and the expression of genes related in to synaptic remodeling/plasticity, or regulated by neuronal activity or the cell cycle were detected by real-time PCR. We found that SAHA attenuated sevoflurane-induced learning and memory impairments in fetal mice. Our findings suggest that SAHA may have potential as a therapeutic agent for preventing or treating the neurotoxicity associated with anesthesia.