Arachidonic acid and lipoxin A4 attenuate alloxan- induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo
Arachidonic acid and lipoxin A4 attenuate alloxan- induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo
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DOI：
10.1002/biof.1336
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发表时间：
2017-03-01
期刊：
影响因子：
6
通讯作者：
Das, Undurti N.
中科院分区：
文献类型：
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作者：
Gundala, Naveen K. V.;Naidu, Vegi G. M.;Das, Undurti N.
目的：我们研究了多不饱和脂肪酸（PUFAs）是否可以保护大鼠胰岛素瘤（RIN 5 F）细胞对四氧嘧啶诱导的细胞凋亡在体外和1型糖尿病（1型DM）在体内，如果是这样，这种有益的行动的机制。材料与方法：采用RIN 5 F细胞进行体外研究，并在Wistar大鼠中进行体内研究。研究了PUFA、环氧合酶和脂氧合酶抑制剂、各种类二十烷酸和PUFA代谢物：脂氧素A4（LXA 4）、resolvin D2和保护素对四氧嘧啶诱导的RIN 5 F细胞和1型DM细胞毒性的影响。检测RIN 5 F细胞PDX 1、P65 NF-kB和IKB的表达，胰腺组织Nrf 2、GLUT 2、COX 2、iNOS蛋白水平，以及血糖、胰岛素、肿瘤坏死因子-α、抗氧化剂、脂质过氧化物和一氧化氮水平。结果如下：其中，花生四烯酸（AA）被认为是最有效的对抗四氧嘧啶诱导的细胞毒性RIN 5 F细胞和预防1型糖尿病。环氧合酶和脂氧合酶抑制剂在体外和体内都不能阻断AA的有益作用。四氧嘧啶抑制RIN 5 F细胞和四氧嘧啶诱导的1型糖尿病Wistar大鼠LXA 4的产生。AA处理使LXA 4水平在体外和体内均恢复至正常。LXA 4保护RIN 5 F细胞免受四氧嘧啶诱导的细胞毒性，预防1型糖尿病，并恢复Nrf 2，Glut 2，COX 2和iNOS基因的表达和异常的抗氧化剂接近正常。讨论：AA似乎通过增强LXA 4的产生来对抗四氧嘧啶诱导的细胞毒性和1型DM。(C) 2016
Objective: We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. Material and Methods: In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Expression of PDX1, P65 NF-kB and IKB in RIN5F cells and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue and plasma glucose, insulin and tumor necrosis factor-a and antioxidants, lipid peroxides and nitric oxide were measured. Results: Of all, arachidonic acid ( AA) was found to be the most effective against alloxan-induced cytotoxicity to RIN5F cells and preventing type 1 DM. Both cyclo-oxygenase and lipoxygenase inhibitors did not block the beneficial actions of AA in vitro and in vivo. Alloxan inhibited LXA4 production by RIN5F cells and in alloxan-induced type 1 DM Wistar rats. AA-treatment restored LXA4 levels to normal both in vitro and in vivo. LXA4 protected RIN5F cells against alloxan-induced cytotoxicity and prevented type 1 DM and restored expression of Nrf2, Glut2, COX2, and iNOS genes and abnormal antioxidants to near normal. Discussion: AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. (C) 2016