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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
Cigarette smoke exacerbates Acetaminophen-induced liver injury by modulating oxidative stress
and inflammation via JNK signal pathway in mice
Jing Zhao1, Kyuhong Lee2, Moo-Yeol Lee 3 and Bumseok Kim1
1Chonbuk National University, South Korea
2Korea Institute of Toxicology, South Korea
3Dongguk University, South Korea
Acetaminophen (APAP) overdose induces inflammation and oxidative
stress that can lead to severe liver injury. Cigarette smoking is considered
to be a crucial modifiable risk factor for disease and death worldwide. Our
previous data revealed that cigarette 3R4F aggravated APAP-induced liver
injury in a dose-dependent manner. This study aimed to investigate the
effects of commercial cigarette A on the progression of APAP-induced acute
liver injury. Seven-week-old C57BL/6 mice were exposed to cigarette A
(300, 600 μg/L) or standard cigarette 3R4F (600 μg/L) or fresh air for 2 hours
once daily and 5 days per week. After 4 weeks, mice were intra-peritoneally
injected with PBS or APAP (500 mg/kg). Eight hours later the mice were euthanized and blood and tissues were collected for
analysis. The results showed that cigarette smoke exposure significantly increased APAP-induced liver injury by increasing
serum ALT and AST levels, exacerbated hepatic pathological damages with inflammatory cell infiltration and hepatocellular
apoptosis and accompanied by up-regulated inflammatory mediators including tumor necrosis factor (TNF-α) and interleukin
(IL)-1β. Cigarette smoke could increase the expressions of cytochrome P450 (CYP) 2E1 and 1A2 which couldmetabolize a large
number of compounds in liver and lead to the down-regulation of antioxidant such as glutathione peroxidase (GSH-Px) and
heme oxygenase-1 (HO-1) in APAP treated mice. Furthermore, cigarette smoke exposure obviously increased the activation of
c-Jun N-terminal kinases (JNK) signal induced by APAP. Mice exposed to commercial cigarette A had no significant difference
between those exposed to standard cigarette 3R4F after APAP injection. Overall, these findings suggested that cigarette smoke
exposure could exacerbate APAP-induced hepatotoxicity and possible mechanism might be associated with the activation of
JNK signal pathway.
References
1. Park S, Kim JW, YunH, KimB (2016)Mainstreamcigarette smoke accelerates the progression of nonalcoholic steatohepatitis by
modulating Kupffer cell-mediated hepatocellular apoptosis in adolescent mice. Toxicology Letters; 256: 53-63.
2. de la Monte S M, Tong M, Agarwal A R, Cadenas E (2016) Tobacco Smoke-Induced Hepatic Injury with Steatosis,
Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling. International Journal of Clinical and
Experimental Pathology; 6(2).
3. Hanawa N, Shinohara M, Saberi B, Kaplowitz N (2008) Role of JNK translocation to mitochondria leading to inhibition
of mitochondria bioenergetics in acetaminophen-induced liver injury. Journal of Biological Chemistry; 283(20): 13565-77.
4. Yoon E, Babar A, Choudhary M, Pyrsopoulos N (2016) Acetaminophen-Induced Hepatotoxicity: a Comprehensive
Update. Journal of Clinical and Translational Hepatology; 4(2): 131-42.
5. Cubero F J, Zoubek M E, Hu W, Trautwein C (2016) Combined Activities of JNK1 and JNK2 in Hepatocytes Protect
Against Toxic Liver Injury. Gastroenterology; 150(4): 968-81.
Biography
Jing Zhao is currently a Doctoral student of Veterinary Pathology in Chonbuk National University of South Korea and has received her Master’s degree of Veterinary
Medicine in China in July 2015. Her experiments focus on the liver diseases and damages in mice, including Acetaminophen-induced liver injury and Concanavalin
A-induced liver injury.
Jing Zhao et al., Toxicol Open Access 2018, Volume 4
DOI: 10.4172/2476-2067-C1-006