Toxicology in vitro : an international journal published in association with BIBRA
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β-Ionone, a precursor of carotenoids, possesses a variety of biological properties such as anti-cancerous, anti-mutagenic and anti-microbial activity. Nevertheless, anti-inflammatory effects of β-ionone remain unknown. In this study, we investigated whether ION attenuates the expression of lipopolysaccharide (LPS)-induced pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) in BV2 microglia cells. ⋯ We also found that LPS-induced NF-κB activation is significantly regulated through inhibition of Akt phosphorylation in the presence of β-ionone. Finally, we showed that β-ionone substantially inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, p38 and JNK, which are closely related to regulation of pro-inflammatory mediator secretion. Taken together, these data imply that β-ionone regulates LPS-induced NF-κB-dependent inflammatory pathways through suppression of Akt and MAPK activation.
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β-Cell apoptosis is considered to be a major cause of loss of β cells in diabetes. Geniposide could prevent oxidative stress-induced neuron apoptosis, and improved glucose stimulated insulin secretion by activating glucagon-like peptide 1 receptor (GLP-1R) in INS-1 cells. Here we have investigated whether geniposide can exert a direct effect against pancreatic β-cell lipoapoptosis. ⋯ Long-term incubation with palmitate decreased GLP-1R expression in INS-1 cells, and exendin (9-39), an antagonist for GLP-1R, inhibited the effect of geniposide on palmitate-induced apoptosis in INS-1 cells. Moreover, geniposide also improved the impairment of GLP-1R signaling through enhancing the phosphorylation of Akt and Foxo1, and increased the expression of PDX-1 in palmitate-treated INS-1 cells. These results suggest that geniposide inhibits early stage of lipotoxicity-induced β-cell apoptosis, and GLP-1R plays a critical role in geniposide counteracting the action of lipotoxicity in INS-1 pancreatic β cells.
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Inflammation has recently been implicated as a critical mechanism responsible for neurodegenerative diseases. In this study, paeonol (1-(2-hydroxy-4-methoxyphenyl)ethanone) isolated from the sea horse Hippocampus kuda Bleeler was studied as an agent to suppress LPS induced activation of BV-2 microglial and RAW264.7 macrophage cells. The results obtained showed that paeonol significantly suppressed LPS induced release of pro-inflammatory products such as nitric oxide (NO), prostaglandin E2 (PGE(2)), and cytokines; tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). ⋯ Moreover, it suppressed the phosphorylation of mitogen activated protein kinase (MAPK) pathway molecules; c-Jun N-terminal kinases (JNK) and p38 in both cell lines. Collectively these results indicate that paeonol blocked the LPS stimulated inflammatory responses in BV-2 and RAW264.7 cells via modulating MAPK and NF-κB signaling pathways. Therefore, paeonol could be a promising candidate to be used in neuro-inflammatory therapy.
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Mechanisms by which age modifies general anesthetic requirements remain uncertain. In order to examine the age-related modification of general anesthetics in the central nervous system, we have studied the effects of thiopental and sevoflurane on hippocampal synaptic transmission in young and elderly rats. Field potentials of area CA1 were electrically elicited in hippocampal slices from young (4-month) and elderly (2-year) male Wistat rats. ⋯ Corresponding experiments revealed (a) that the duration of recurrent inhibition was more prolonged by thiopental in young compared to elderly animals and (b) that thiopental enhanced the γ-amino-butyric acid (GABA) release from pre-synaptic terminals in an age-dependent manner. The thiopental actions on GABA discharge from pre-synaptic terminals appear to be responsible for the observed difference between young and elderly animals. The age-dependent reduction in neurotransmitter stores in pre-synaptic terminals may explain the age-related alterations in general anesthetic actions.
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Fentanyl in a rate controlling membrane (RCM) transdermal patch form has been available since the early 1990s for outpatient management of chronic pain. Fatalities associated with misuse or overuse of fentanyl patches have been reported. Concerns have also been raised about the possibility that defects in such patches may result in leaking of the reservoir of the patch onto patients' skin and consequent overdose. ⋯ Assuming spreading of leaked gel over an area of 100 cm(2), this would result in a plasma level of 0.6 ng/mL. The anticipated plasma levels from a 100 μg/h patch are known to be approximately 2.5 ng/ml. Thus, the maximum increase in the plasma levels from a patch which leaks gel is calculated to be, at most, about 25%.