Tiron protects against nicotine-induced lung and liver injury through antioxidant and anti-inflammatory actions in rats in vivo

Tobacco smoking is a major health problem associated with lung and liver damage. Lung and liver damage secondary to tobacco smoking is mediated through nicotine-induced oxidative stress. Therefore, we hypothesized that antioxidant treatment with tiron may improve nicotine-induced lung and liver damage. Rats were divided into six groups, a control, nicotine (10 mg/kg/day, i.p.; for 8 weeks) and tiron (100 or 200 mg/kg/day, i.p.; for 8 weeks) with or without nicotine administration. Tiron improved survival rate and attenuated lung and liver damage as reflected by decreased total and differential cell counts, lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF) and decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in serum; also histopathological examination confirmed the protective effect of tiron in lung and liver tissues of nicotine treated rats. Tiron attenuated dyslipidemia, which is associated with nicotine. These ameliorative effects of tiron may be mainly due to its antioxidant effect as proved by a significant decrease in malondialdehyde (MDA) content, reactive oxygen species (ROS) and total nitrite/nitrate (NOx) levels, and increase in reduced glutathione (GSH) level, catalase (CAT) and superoxide dismutase (SOD) activities. This is likely related to suppression of protein levels of NADPH oxidase enzyme (NOX1), inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α); and up-regulation of protein levels of nuclear factor erythroid-2 (Nrf2). This makes tiron (synthetic analogue of vitamin E) good candidate for future use to minimize nicotine's hazards among smokers.