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Volume 4 Toxicology: Open Access
ISSN: 2476-2067 Toxicology Congress 2018
March 12-14, 2018
March 12-14, 2018 Singapore
14th World Congress on
Toxicology and Pharmacology
Nicotine attenuates concanavalin A-induced hepatic injury by regulating Kupffer cells in mice
Jing Qi, Jing Zhao, Hyuneui Jeong and Bumseok Kim
Chonbuk National University, South Korea
Nicotine, a major constituent of cigarette smoke, is a potent parasympathomimetic
alkaloid found in the nightshade family of plants. Acute liver failure (ALF), known as
a rapid and severe clinical syndrome, can induce multiple organ dysfunction and failure.
This study aimed to investigate the effects of nicotine on concanavalin A (Con A) induced
autoimmune hepatitis in mice and to elucidate its underlying molecular mechanisms.
Autoimmune hepatitis was induced by the intravenous administration of Con A (15 mg/kg)
to healthy BALB/c male mice and nicotine (0.5 mg/kg and 1 mg/kg) was intra-peritoneally
injected before the challenge with Con A. Eight hours later the mice were euthanized
and blood and tissues were collected for analysis. The present study showed that nicotine
pretreatment significantly decreased the elevated serum alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) and ameliorated hepatic pathological damage and necrosis.
In addition, nicotine treatment markedly suppressed the secretion of pro-inflammatory
cytokines and chemokines including tumor necrosis factor-a (TNF-a), interferon (IFN)-γ and interleukin (IL)-4. Furthermore,
nicotine down-regulated the activation of NF-kB signal in Con A-treated mouse livers. Since Kupffer cells have been known as
a crucial component in the initial part of pathogenesis of ALF, our present study confirmed that depletion of Kupffer cells by
liposomal clodronate abolished the protective effects of nicotine against Con A-induced hepatitis, as shown by the similar levels
of serum aminotransferase levels and pro-inflammatory cytokines with or without nicotine treatment in Con A treated mouse
livers. In the primary Kupffer cells, nicotine ameliorated inflammatory cytokines and regulated the expression of NF-kB signal.
Consistent with the above findings, this study suggested that nicotine could attenuate Con A-induced autoimmune hepatitis
and possible mechanism might be associated with the inhibition of Kupffer cells activation through NF-kB signal pathway.
Recent Publications
1. Park S, KimJW, YunH, KimB (2016)Mainstreamcigarette smoke accelerates the progressionof nonalcoholic steatohepatitis
by modulating Kupffer cell-mediated hepatocellular apoptosis in adolescent mice. Toxicology Letters; 256: 53-63.
2. Yang Q, Liu Y, Shi Y, Chen Z (2013) The role of intracellular high-mobility group box 1 in the early activation of Kupffer
cells and the development of Con A-induced acute liver failure. Immunobiology; 218(10): 1284-92.
3. Kimura K, Tanida M, Nagata N, Inoue H (2016) Central Insulin Action Activates Kupffer Cells by Suppressing Hepatic
Vagal Activation via the Nicotinic Alpha 7 Acetylcholine Receptor. Cell Reports; 14(10): 2362-74.
4. Schwabe RF, Brenner DA (2006) Mechanisms of Liver Injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and
ROS pathways. American journal of Physiology-Gastrointestinal and Liver Physiology ; 290(4): G583-9.
Biography
Jing Qi is a currently pursuing MBBS in Veterinary Pathology from Chonbuk National University of South Korea and has completed her Master’s degree of
Veterinary Medicine in China in June 2016. She is mainly researching on hepatotoxicity induced by medicine or metabolism in the mouse model.
Jing Qi et al., Toxicol Open Access 2018, Volume 4
DOI: 10.4172/2476-2067-C1-006