Bone metabolism and oxidative stress in postmenopausal rats with iron overload

被引:145
作者
Isomura, H
Fujie, K
Shibata, K
Inoue, N
Iizuka, T
Takebe, G
Takahashi, K
Nishihira, J
Izumi, H
Sakamoto, W
机构
[1] Hokkaido Univ, Sch Dent, Dept Biochem, Kita Ku, Sapporo, Hokkaido 060, Japan
[2] Hokkaido Univ, Sch Dent, Dept Geriator Stomatol, Sapporo, Hokkaido 060, Japan
[3] Hokkaido Univ, Sch Dent, Dept Oral Pathol, Sapporo, Hokkaido 060, Japan
[4] Hokkaido Univ, Sch Dent, Fac Pharmaceut Sci, Sapporo, Hokkaido 060, Japan
[5] Hokkaido Univ, Sch Dent, Dept Oral Physiol, Ishikari, Hokkaido 061, Japan
关键词
iron lactate; oxidative stress; glutathione peroxidase; TGF-beta; 1; bone metabolism;
D O I
10.1016/j.tox.2003.12.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Osteoporosis is associated with many etiological causes such as nutrition, cytokines, hormones, and aging. Recently, reactive oxygen species (ROS) are considered to be responsible for the aging process and osteoporosis. We investigated the relationship between ROS and bone metabolism in young female and postmenopausal rats, by using dietary iron overload and several indices including bone metabolic markers, oxidative stress and antioxidant markers, and cytokines. Postmenopausal rats exhibited significant decreases in serum alkaline phosphatase activity and the level of osteocalcin as bone formation markers compared with young female rats; however, urinary excretion of deoxypyridinoline, a bone resorption marker, did not change. On the other hand, a 5% iron lactate diet for 4 weeks in postmenopausal rats led to significantly increased excretion of urinary deoxypyridinoline,and 8-hydroxy-2'-deoxyguanosine (8-OHdG) but not serum alkaline phosphatase activity. Interestingly, the diet induced significant increases of serum osteopontin and TGF-beta1, augumenting osteoclast-mediated bone resorption through the RANK/RANKL pathway [J. Clin. Invest. 112 (2003) 181]. TGF-beta1 showed a negative correlation with serum glutathione peroxidase (GPx) activity (r = -0.674, P < 0.003), but a positive correlation with the serum iron level (r = 0.836, P < 0.0001). Taken together, these results suggest for the first time that oxidative stress could be involved in the pathogenesis of metabolic bone diseases such as osteoporosis as demonstrated by analysis of the relationship between bone metabolism and oxidative stress. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:93 / 100
页数:8
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