Inhibitory effect of vitamin E on proinflammatory cytokines-and endotoxin-induced nitric oxide release in alveolar macrophages
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文摘
Nitric oxide is thought to be an important modulator of various functions in normal and inflamed airways. In the present study, we evaluated the effects of high vitamin E (250 mg and 1250 mg α-tocopheryl acetate (TA)/kg diet/10 days) on nitric oxide (NO) release by alveolar macrophages (AMs) in response to lipopolysaccharide (LPS), interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α). LPS and IL-1β treatment (1-10 μg/ml) enhanced NO release in AMs from control animals fed on 50 mg vitamin E/kg diet in a concentration dependent manner. However, this enhancement of NO was attenuated in the AMs of animals fed with 250 mg or 1250 mg vitamin E/kg diet. TNF-α had no effect in eliciting the release of NO in AMs obtained either from control or from hyper vitamin E fed animals. Further, LPS (1-10 μg/ml) enhanced the inducible nitric oxide synthase (iNOS) activity of AMs of control group and TA-fed animals almost to equal extent. Similarly, LPS-induced formation of N-nitrosamine (N-nitroso-L-[14C]-proline) in AMs of control and TA-supplemented animals were not different statistically. On the other hand, in vitro addition of vitamin E (200 μM) in AMs of control animals, when triggered with 10 μg LPS/ml, caused a significant decrease in N-nitroso-L-[14C]-proline formation. It seems that high doses of TA in diet may play a role in reducing the lipopolysaccharide and proinflammatory cytokines-induced NO-mediated damage by AMs.

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