Detrimental effects of nicotine on thioacetamide-induced liver injury in mice

Zixiong Zhou, Surim Park, Jong Won Kim, Jing Zhao, Moo Yeol Lee, Kyung Chul Choi, Chae Woong Lim, Bumseok Kim

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Aim: Nicotine exerts a number of physiological effects. The purpose of this study was to determine the effects of nicotine on thioacetamide (TAA)-induced liver fibrosis in mice. Materials and methods: For in vivo experiments, hepatic fibrosis was induced by TAA (0.25 g/kg, i.p.) three times a week for 6 weeks. Mice of TAA treated groups were administered daily with distilled water and nicotine (50 or 100 μg/mL) via gastrogavage throughout the experimental period. For in vitro experiments, HepG2 (human liver cancer cell line) and LX-2 (human hepatic stellate cell line) were used to determine oxidative stress and fibrosis, respectively. Results: Compared to control groups, TAA treated groups had significantly differences in serum alanine transferase and aspartate aminotransferase levels and nicotine accentuated liver injury. Moreover, nicotine increased the mRNA levels of TAA-induced transforming growth factor-β (TGF-β) and collagen type I alpha 1 in the liver. Nicotine also increased TAA-induced oxidative stress. Histological examination confirmed that nicotine aggravated the degree of fibrosis caused by TAA treatment. Additionally, nicotine enhanced hepatic stellate cell activation via promoting the expression of α-smooth muscle actin. Conclusions: Oral administration of nicotine significantly aggravated TAA-induced hepatic fibrosis in mice through enhancing TGF-β secretion and TAA-induced oxidative stress. The increase in TGF-β levels might be associated with the strengthening of oxidative processes, subsequently leading to increased hepatic stellate cell activation and extracellular matrix deposition. These results suggest that patients with liver disease should be advised to abandon smoking since nicotine may exacerbate hepatic fibrosis.

Original languageEnglish
Pages (from-to)501-510
Number of pages10
JournalToxicology Mechanisms and Methods
Volume27
Issue number7
DOIs
StatePublished - 2 Sep 2017

Keywords

  • fibrosis
  • liver
  • mice
  • nicotine
  • Thioacetamide

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