Sumoski W, Baquerizo H, Rabinovitch A
Department of Medicine, University of Alberta, Edmonton, Canada.
Diabetologia. 1989 Nov;32(11):792-6. doi: 10.1007/BF00264909.
A possible role for oxygen free radicals in mediating the cytotoxic effects of cytokines in islets was sought by the use of agents that scavenge free radicals. Rat islet cell monolayer cultures were incubated for 6 days with t-butylhydroperoxide, alloxan, streptozotocin, or the cytokines, interleukin 1, tumour necrosis factor, and interferon gamma, without and together with the oxygen free radical scavenger combination of dimethylthiourea and citiolone, and islet cell lysis was measured in a 51chromium cytotoxicity assay. The free radical scavengers significantly inhibited the islet cell cytotoxic effects of t-butylhydroperoxide and alloxan, but not streptozotocin. Similarly, the cytotoxic effects of the cytokine combinations of interleukin 1 plus tumour necrosis factor, interferon gamma plus tumour necrosis factor, and interferon gamma plus interleukin 1 were significantly inhibited by the free radical scavenger combination of dimethylthiourea and citiolone. These results suggest that the cytokine products of macrophages and lymphocytes infiltrating islets in Type 1 (insulin-dependent) diabetes may contribute to B-cell damage by inducing the production of oxygen free radicals in the islet cells.
通过使用清除自由基的试剂，研究了氧自由基在介导细胞因子对胰岛细胞毒性作用中可能扮演的角色。将大鼠胰岛细胞单层培养物分别与叔丁基过氧化氢、四氧嘧啶、链脲佐菌素或细胞因子白细胞介素-1、肿瘤坏死因子和干扰素-γ共同孵育6天，其中一组不添加二甲硫脲和依地酸二钠钙的氧自由基清除剂组合，另一组添加该组合，然后通过51铬细胞毒性试验测定胰岛细胞裂解情况。自由基清除剂显著抑制了叔丁基过氧化氢和四氧嘧啶对胰岛细胞的细胞毒性作用，但对链脲佐菌素无此作用。同样，二甲硫脲和依地酸二钠钙的自由基清除剂组合也显著抑制了白细胞介素-1加肿瘤坏死因子、干扰素-γ加肿瘤坏死因子以及干扰素-γ加白细胞介素-1等细胞因子组合的细胞毒性作用。这些结果表明，1型（胰岛素依赖型）糖尿病中浸润胰岛的巨噬细胞和淋巴细胞产生的细胞因子，可能通过诱导胰岛细胞产生氧自由基，从而导致β细胞损伤。
