title: Inhibitory effect of vitamin E on proinflammatory cytokines-and endotoxin-induced nitric oxide release in alveolar macrophages.
abstract: 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 alpha-tocopheryl acetate (TA)/kg diet/10 days) on nitric oxide (NO(.)) release by alveolar macrophages (AMs) in response to lipopolysaccharide (LPS), interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha). LPS and IL-1beta treatment (1-10 microg/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-alpha 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 microg/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-[(14)C]-proline) in AMs of control and TA-supplemented animals were not different statistically. On the other hand, in vitro addition of vitamin E (200 microM) in AMs of control animals, when triggered with 10 microg LPS/ml, caused a significant decrease in N-nitroso-L-[(14)C]-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.
authors.affiliation: Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. klkhanduja@rediffmail.com
authors.forename: Krishan Lal
authors.initials: KL
authors.lastname: Khanduja
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Avti
authors.forename: Surender
authors.initials: S
authors.lastname: Kumar
authors.forename: Vandana
authors.initials: V
authors.lastname: Pathania
authors.forename: Chander Mohan
authors.initials: CM
authors.lastname: Pathak
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D004032:Diet; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009602:Nitrosamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009602:Nitrosamines; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C010259:nitrosoproline