The effects of gallium nitrate on osteopenia induced by ovariectomy and a low-calcium diet in rats

Lawrence S. Stern , Velimir Matkovic , Steven E. Weisbrode , Glen Apseloff , Dale R. Shepard , Dennis C. Mays , Nicholas Gerber
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引用次数: 12

Abstract

The effects of gallium nitrate (GN) were evaluated on osteopenia induced by ovariectomy (OVX) and a low-calcium diet (LCD) in Sprague-Dawley rats. Twenty-five rats (300–400 g) were randomized into four groups of 5–7 animals: (I) OVX LCD treated with GN for 22 weeks; (II) OVX LCD treated with GN for 10 weeks; (III) OVX LCD treated with saline; and (IV) sham-operated (SO), normal diet, treated with saline. GN-treated rats received a 30-mg/kg subcutaneous single dose of elemental gallium, followed by 10 mg/kg per week, whereas control animals received an equal volume of saline. All animals were euthanized at 22 weeks. Measurements of bone density and histomorphometry, performed on the proximal portion of the tibia, indicated significant bone loss in all OVX LCD animals. GN-treated rats in group I gained significantly less weight than those in the other groups, and their blood urea nitrogen increased, suggesting a nephrotoxic effect. After discontinuation of GN, rats in group II gained weight at the same rate as those which had received only saline. Bone formation rates in the GN-treated rats were double those of the saline-treated OVX animals and more than 10 times those of SO controls. Although the bone formation rate in GN-treated rats increased, GN had no effect in preventing the loss of bone surface, density and volume induced by OVX LCD. These findings suggest that although GN may enhance osteoblastic activity, this agent alone does not appear effective in the prevention of bone loss induced by OVX LCD.

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硝酸镓对大鼠卵巢切除及低钙饮食所致骨质减少的影响
探讨硝酸镓(GN)对Sprague-Dawley大鼠卵巢切除(OVX)和低钙饮食(LCD)所致骨质减少的影响。取25只大鼠,每只300 ~ 400 g,随机分为4组,每组5 ~ 7只:(1)用GN治疗OVX LCD 22周;(II) GN治疗OVX LCD 10周;(III)生理盐水处理OVX LCD;(IV)假手术(SO),正常饮食,生理盐水处理。经gn处理的大鼠皮下注射单剂量元素镓30 mg/kg,随后每周注射10 mg/kg,而对照动物则注射等量生理盐水。所有动物在22周时被安乐死。在胫骨近端进行的骨密度和组织形态测量显示,所有OVX LCD动物的骨质流失都很严重。与其他组相比,1组服用gn的大鼠体重明显增加,血尿素氮增加,提示肾毒性作用。停用GN后,II组大鼠的体重增加速度与只接受生理盐水的大鼠相同。gn处理的大鼠的骨形成率是盐水处理的OVX动物的两倍,是SO对照的10倍以上。虽然GN处理的大鼠骨形成率增加,但GN对OVX LCD诱导的骨表面、密度和体积损失没有作用。这些发现表明,虽然GN可以增强成骨细胞活性,但单独使用这种药物似乎不能有效预防OVX LCD诱导的骨质流失。
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