PMID- 32937159 OWN - NLM STAT- MEDLINE DCOM- 20201127 LR - 20201127 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 260 DP - 2020 Nov 1 TI - Tiron protects against nicotine-induced lung and liver injury through antioxidant and anti-inflammatory actions in rats in vivo. PG - 118426 LID - S0024-3205(20)31179-6 [pii] LID - 10.1016/j.lfs.2020.118426 [doi] AB - AIMS: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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-kappaB) and tumor necrosis factor alpha (TNF-alpha); and up-regulation of protein levels of nuclear factor erythroid-2 (Nrf2). SIGNIFICANCE: This makes tiron (synthetic analogue of vitamin E) good candidate for future use to minimize nicotine's hazards among smokers. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Khaled, Shimaa AU - Khaled S AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Horus University, Egypt. Electronic address: shimaa_khaled95@yahoo.com. FAU - Makled, Mirhan N AU - Makled MN AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. FAU - Nader, Manar A AU - Nader MA AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. LA - eng PT - Journal Article DEP - 20200913 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Antioxidants) RN - 0 (Enzymes) RN - 0 (Lipids) RN - 0 (NF-kappa B) RN - 0 (Protective Agents) RN - 4X87R5T106 (1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt) RN - 6M3C89ZY6R (Nicotine) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - EC 1.6.3.- (NADPH Oxidase 1) RN - EC 1.6.3.- (NOX1 protein, rat) SB - IM MH - 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/*pharmacology MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/pharmacology MH - Antioxidants/*pharmacology MH - Body Weight/drug effects MH - Bronchoalveolar Lavage Fluid/chemistry MH - Cell Count MH - Chemical and Drug Induced Liver Injury/etiology/mortality/pathology/*prevention & control MH - Enzymes/blood MH - L-Lactate Dehydrogenase/metabolism MH - Lipids/blood MH - Lung Injury/chemically induced/mortality/pathology/*prevention & control MH - Male MH - NADPH Oxidase 1/blood/metabolism MH - NF-kappa B/blood/metabolism MH - Nicotine/*toxicity MH - Nitric Oxide Synthase Type II/metabolism MH - Protective Agents/pharmacology MH - Rats, Sprague-Dawley OTO - NOTNLM OT - NF-kappaB OT - Nicotine OT - Nrf2 OT - Oxidative stress OT - Tiron OT - iNOS EDAT- 2020/09/17 06:00 MHDA- 2020/11/28 06:00 CRDT- 2020/09/16 20:07 PHST- 2020/05/30 00:00 [received] PHST- 2020/09/01 00:00 [revised] PHST- 2020/09/09 00:00 [accepted] PHST- 2020/09/17 06:00 [pubmed] PHST- 2020/11/28 06:00 [medline] PHST- 2020/09/16 20:07 [entrez] AID - S0024-3205(20)31179-6 [pii] AID - 10.1016/j.lfs.2020.118426 [doi] PST - ppublish SO - Life Sci. 2020 Nov 1;260:118426. doi: 10.1016/j.lfs.2020.118426. Epub 2020 Sep 13.