title: Dietary fish oil exacerbates concanavalin A induced hepatitis through promoting hepatocyte apoptosis and altering immune cell populations.
abstract: 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-α and IFN-γ 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.
authors.affiliation: Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xia
authors.forename: Mutian
authors.initials: M
authors.lastname: Han
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Cheng
authors.forename: Yetao
authors.initials: Y
authors.lastname: Qiang
authors.forename: Shuiyun
authors.initials: S
authors.lastname: Wu
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhang
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Qixiang
authors.initials: Q
authors.lastname: Shao
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D039481:CD11b Antigen; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology*; D003208:Concanavalin A / Q000494:pharmacology*; D019587:Dietary Supplements / Q000009:adverse effects; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects*; D005395:Fish Oils / Q000009:adverse effects* / Q000737:chemistry; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000473:pathology*; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D006836:Hydro-Lyases / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000473:pathology; D017493:Leukocyte Common Antigens; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D000410:Alanine Transaminase; D017493:Leukocyte Common Antigens; D006836:Hydro-Lyases; C045581:lactate dehydratase