Immunomodulatory effects of high-dose α-tocopherol acetate on mice subjected to sidestream cigarette smoke

Shengjun Wang, Nina N. Sun, Jin Zhang, Ronald R. Watson, Mark L. Witten

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Several recent epidemiological investigations raise serious questions about the health effects of high-dose supplements of Vitamin E (VE) in cigarette smokers. To examine these findings, a total of 96 C57BL/6 mice were randomly assigned to eight groups in a 2×4 factorial design (smoke vs. sham smoke and normal diet vs. 3 VE supplements). The mice were exposed to sidestream cigarette smoke (SSCS), at 0.4 mg total particulate matter/m3 air, from standard research cigarettes (1R4)/day or filtered room air at 30 min/day, 5 days/week, for 9 weeks through a nose-only exposure chamber. The American Institute of Nutrition 93G purified rodent diet was modulated with 75 (regular diet, 1-fold), 1050 (15-fold), 5550 (75-fold), and 11 175 (150-fold) IU dl-α-tocopherol acetate (α-TA)/kg as VE supplementation and provided ad libitum at an average intake rate of 4.11 g diet/mouse/day. This result demonstrated that SSCS exposure results in lung dysfunction, as indicated by a decrease of pulmonary dynamic compliance (Cdyn) and increase of lung resistance (RL), and body weight loss in mice fed with regular diet. These changes accompanied with increases of bronchoalveolar lavage (BAL) concentrations of cytokines interleukin (IL)-1β, IL-4 and IFN-γ, as well as hepatic lipid peroxidation. However, supplemental α-TA at the doses of ≥1050 IU/kg diet prevented the SSCS-induced body weight loss and lung dysfunction. α-TA at ≥5550 IU/kg significantly increased BAL levels of IL-2 and IL-4 in both the sham SSCS and the SSCS groups. Given at 5550 IU α-TA/kg, but not higher, mice elevated BAL IL-1β level if they were exposed to SSCS. Hepatic lipid peroxidation was decreased in a dose-dependent fashion with different α-TA supplements in both the sham SSCS and SSCS groups. Neither SSCS nor α-TA had an effect on lung permeability, BAL IL-6, splenic T and B lymphocyte proliferation and their T helper (Th)1 and Th2 cytokines measured among all groups. Data suggest that supplemental α-TA may be needed to counteract SSCS-induced oxidative stress, but that potential side effects introduced by high dosage of this synthetic compound should be considered.

Original languageEnglish (US)
Pages (from-to)235-245
Number of pages11
JournalToxicology
Volume175
Issue number1-3
DOIs
StatePublished - Jun 14 2002

Keywords

  • Cytokines
  • Lipid peroxidation
  • Lung function
  • Lymphocyte proliferation
  • Respiratory permeability
  • Sidestream cigarette smoke
  • α-Tocopherol

ASJC Scopus subject areas

  • Toxicology

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