Dietary fish oil exacerbates concanavalin A induced hepatitis through promoting hepatocyte apoptosis and altering immune cell populations

作者：Xia Sheng^*; Han Mutian; Li Xiaoping; Cheng Lu; Qiang Yetao; Wu Shuiyun; Zhang Miaomiao; Xu Huaxi; Liu Xia; Shao Qixiang

来源：Journal of Toxicological Sciences, 2014, 39(2): 179-190.

DOI：10.2131/jts.39.179

• Hepatitis
• Concanavalin A
• Lymphocyte
• Myeloid cell
• Fatty acids
• Fish oil

The development of hepatitis is associated with the infiltration and activation of immune cells in liver. N-3 polyunsaturated fatty acids (n-3 PUFAs) rich fish oil (FO) is used to prevent and treat inflammatory diseases. But, the effects of dietary FO on autoimmune hepatitis remain largely unknown. In this study, Concanavalin A (Con A) induced hepatitis was used to evaluate the actions of dietary FO. Unexpectedly, 2-week FO treatment had not shown any protection, on the contrary, exacerbated liver injury in this hepatitis model. The levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) statistically increased from 10,501 +/- 2,154 and 30,394 +/- 2,420 in low fat diet (LFD)/Con A group to 17,579 +/- 693 and 49,439 +/- 4,628 in FO/Con A group. Simultaneously, FO diet induced more necrotic liver tissues and apoptotic hepatocytes, and up-regulated the hepatic expression of TNF-alpha and IFN-gamma after Con A challenge. Interestingly, FO promoted severe liver injury was accompanied by decreasing the percentage of CD4(+) T cell, NK1.1(+) cells and CD8(+) T cells in CD45(+) liver non-parenchymal hepatic cells (NPCs) through inducing apoptosis. Further experiments declared 2-week FO diet intake firstly increased the proportion of CD11b(+)Gr-1(hi) neutrophils in liver, but then dramatically expanded CD11b(+)Gr-1(int) inflammatory monocytes population after Con A administration. Collectively, our study indicated that high FO intake not only aggravated liver injury, but also altered the population of immune cells in liver. Thus, these results indicated that when dietary FO was used to benefit health in autoimmune diseases, its potential risks of side effect also need paying close attention.

• 出版日期2014-4
• 单位江苏大学