Jing Zhao
Chonbuk National University, South Korea
Title: Cigarette smoke exacerbates Acetaminophen-induced liver injury by modulating oxidative stress and inflammation via JNK signal pathway in mice
Biography
Biography: Jing Zhao
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 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 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.