Bisphosphonate-induced gastrointestinal mucosal injury is mediated by mitochondrial superoxide production and lipid peroxidation.
Bisphosphonate-induced gastrointestinal mucosal injury is mediated by mitochondrial superoxide production and lipid peroxidation.
复制标题
DOI：
10.3164/jcbn.12-41
复制
发表时间：
2012-11
影响因子：
2.4
通讯作者：
Hyodo I
中科院分区：
文献类型：
--
作者：
Nagano Y;Matsui H;Shimokawa O;Hirayama A;Nakamura Y;Tamura M;Rai K;Kaneko T;Hyodo I
双膦酸盐如阿仑膦酸盐和利塞膦酸盐常用于治疗绝经后骨质疏松症。它们具有胃肠道不良反应，如胃和小肠的糜烂和溃疡。然而，详细的生物学机制仍有待阐明。由于阿仑膦酸钠被认为会增加非甾体抗炎药相关胃病的风险，我们假设双膦酸盐和非甾体抗炎药在胃肠道粘膜中具有相同的病理生理机制：双膦酸盐可能通过诱导线粒体超氧化物的产生来诱导细胞脂质过氧化。我们还假设，抗溃疡药物香叶基香叶基丙酮可能通过减少超氧化物的产生来防止脂质过氧化。我们用阿仑膦酸钠或利塞膦酸钠处理胃RGM1细胞和小肠IEC 6细胞，用特异性荧光染料检测细胞损伤、脂质过氧化和超氧化物的产生，并用电子顺磁共振光谱检测超氧化物的产生。结果表明，双膦酸盐确实诱导细胞损伤，细胞脂质过氧化和超氧化物的产生。我们还表明，香叶基香叶基丙酮的预处理减少超氧化物的产生，防止细胞脂质过氧化。这些结果表明，双膦酸盐，像非甾体抗炎药，诱导脂质过氧化反应，通过产生线粒体超氧化物，这是防止香叶基香叶基丙酮。
Bisphosphonates such as alendronate and risedronate are commonly used for the treatment of postmenopausal osteoporosis. They have the gastrointestinal adverse effects such as erosions and ulcers in stomach and small intestine. However, the detailed biological mechanism remains to be elucidated. Since alendronate is suggested to increase the risk of non-steroidal anti-inflammatory drug-related gastropathy, we hypothesized that bisphosphonates and non-steroidal anti-inflammatory drugs have the same pathophysiological mechanisms in gastrointestinal mucosa: Bisphosphonates may induce cellular lipid peroxidation by inducing the production of mitochondrial superoxide. We also hypothesized that geranylgeranylacetone, an antiulcer drug, may prevent lipid peroxidation by reducing superoxide production. We treated gastric RGM1 cells and small intestinal IEC6 cells with alendronate or risedronate, and examined cellular injury, lipid peroxidation and superoxide production with specific fluorescent dyes, and underwent electron paramagnetic resonance spectroscopy to detect the production of superoxide in vitro. The results indicated that bisphosphonates indeed induced cellular injury, cellular lipid peroxidation, and superoxide production. We also demonstrated that the pretreatment of geranylgeranylacetone decreased superoxide production and prevented cellular lipid peroxidation. These results suggested that bisphosphonates, like non-steroidal anti-inflammatory drugs, induce lipid peroxidation by producing mitochondrial superoxide, which was prevented by geranylgeranylacetone.
登录
查看更多内容
DOI：
10.1111/j.1440-1746.2003.03314.x
发表时间：
2004-05-01
影响因子：
4.1
作者：
Kanatsu, K;Aihara, E;Takeuchi, K
通讯作者：
Takeuchi, K
影响因子：
3.3
作者：
Kamibayashi, Masato;Oowada, Shigeru;Kotake, Yashige
通讯作者：
Kotake, Yashige
影响因子：
--
作者：
Graham, DY;Malaty, HM
通讯作者：
Malaty, HM
影响因子：
6.2
作者：
Luckman, SP;Hughes, DE;Rogers, MJ
通讯作者：
Rogers, MJ
影响因子：
3.5
作者：
Okimoto, Y;Watanabe, A;Noguchi, N
通讯作者：
Noguchi, N