Department of Food Science and Nutrition, Nara Women's University, Japan.
Biol Pharm Bull. 2012;35(6):980-3. doi: 10.1248/bpb.35.980.
Carbon tetrachloride (CCl(4))-induced acute hepatitis is assumed to involve two phases. The initial phase, initiated within 2 h after CCl(4) administration, involves the generation of reactive oxygen species. The second phase is assumed to start about 8 h subsequent to CCl(4) administration and involves the oxidant-induced activation of Kupffer cells, which release various pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We investigated the role of Kupffer cells during CCl(4) intoxication using Nucling-knockout mice (the KO group), in which the number of Kupffer cells is largely reduced. Plasma alanine transaminase and aspartate transaminase levels demonstrated that the liver necrosis during the second phase was significantly alleviated in the KO group compared with that in the wild-type mice (the WT group). Plasma TNF-α concentrations in the WT group significantly increased 24 h after CCl(4) intoxication, whereas those in the KO group did not significantly increase. Plasma IL-6 levels also significantly increased in the WT group 24 h after CCl(4) administration, but those in the KO group did not increase at any time point. These results indicated that excess reactions of Kupffer cells, once primed by oxidants, were involved in the exacerbation of oxidative stress and liver damage during the second phase of CCl(4) intoxication.
四氯化碳（CCl4）诱导的急性肝炎被认为涉及两个阶段。初始阶段发生在 CCl4 给药后 2 小时内，涉及活性氧的生成。第二阶段被认为在 CCl4 给药后约 8 小时开始，涉及氧化剂诱导的枯否细胞激活，枯否细胞释放各种促炎介质，如肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。我们使用 Nucling 敲除小鼠（KO 组）研究了 CCl4 中毒过程中枯否细胞的作用，其中枯否细胞的数量大大减少。血浆丙氨酸转氨酶和天冬氨酸转氨酶水平表明，与野生型小鼠（WT 组）相比，KO 组在第二阶段的肝坏死明显减轻。WT 组血浆 TNF-α浓度在 CCl4 中毒后 24 小时显著增加，而 KO 组则没有显著增加。WT 组血浆 IL-6 水平在 CCl4 给药后 24 小时也显著增加，但 KO 组在任何时间点均未增加。这些结果表明，一旦被氧化剂激活，过量的枯否细胞反应参与了 CCl4 中毒第二阶段氧化应激和肝损伤的加剧。
