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Abstract

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 �¼g/L) or standard cigarette 3R4F (600 �¼g/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-�±) and interleukin (IL)-1�². Cigarette smoke could increase the expressions of cytochrome P450 (CYP) 2E1 and 1A2 which could metabolize 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 J W, Yun H, Kim B (2016) Mainstream cigarette 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.
Email:zhaojing19901230@126.com