Polat Beyzagul, Halici Zekai, Cadirci Elif, Albayrak Abdulmecit, Karakus Emre, Bayir Yasin, Bilen Habip, Sahin Ali, Yuksel Tugba Nurcan
Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
Eur J Pharmacol. 2013 Oct 15;718(1-3):469-74. doi: 10.1016/j.ejphar.2013.07.033. Epub 2013 Jul 30.
Osteoporosis is a high mortality and morbidity ranged skeletal disease and results in high costs of medical care in the European Union. We evaluated the possible protective effect of alpha-lipoic acid (ALA) on rat bone metabolism in ovariectomy and inflammation-mediated osteoporosis models. Groups were designed as: (1) sham; (2) sham+inflammation; (3) ovariectomy (OVX); (4) ovariectomy+ALA-25mg/kg; (5) ovariectomy+ALA-50mg/kg; (6) ovariectomy+inflammation; (7) ovariectomy+inflammation+ALA-25mg/kg; and (8) ovariectomy+inflammation+ALA-50mg/kg groups. OVX groups were allowed to recover for two months. Then, inflammation was induced in inflammation groups by subcutaneous talc injection. ALA-25mg/kg and 50mg/kg were administered to drug groups chronically. The skeletal response was assessed by bone mineral density (BMD), osteopontin and osteocalcin measurements. Pro-inflammatory cytokine measurements (interleukin (IL)-1 beta, interleukin-6, and tumor necrosis factor-alpha) were performed to observe inflammatory process. In OVX, INF and OVX+INF groups, BMD levels were lowest and osteocalcin, osteopontin, IL-1 beta, IL-6, and TNF-alpha levels were highest when compared to sham group. ALA administration increased BMD levels and decreased osteocalcin, osteopontin, IL-1 beta, IL-6, and TNF-alpha levels versus OVX and OVX+INF control groups. Both in senile and postmenopausal osteoporosis, the balance in coupling were destroyed on behalf of bone resorption. ALA had a protective effect on both senile and postmenopausal osteoporosis. The positive effect of this drug in these osteoporosis models might originate from its positive effects on bone turnover markers and cytokine levels. From this perspective, ALA may be a candidate for radical osteoporosis treatment both in senile and postmenopausal types clinically at the end of advanced studies.
骨质疏松症是一种死亡率和发病率较高的骨骼疾病,在欧盟导致高昂的医疗费用。我们评估了α-硫辛酸(ALA)在卵巢切除和炎症介导的骨质疏松症模型中对大鼠骨代谢的可能保护作用。分组如下:(1)假手术组;(2)假手术+炎症组;(3)卵巢切除(OVX)组;(4)卵巢切除+25mg/kg ALA组;(5)卵巢切除+50mg/kg ALA组;(6)卵巢切除+炎症组;(7)卵巢切除+炎症+25mg/kg ALA组;(8)卵巢切除+炎症+50mg/kg ALA组。OVX组让其恢复两个月。然后,通过皮下注射滑石粉在炎症组诱导炎症。25mg/kg和50mg/kg的ALA长期给予药物组。通过骨密度(BMD)、骨桥蛋白和骨钙素测量评估骨骼反应。进行促炎细胞因子测量(白细胞介素(IL)-1β、白细胞介素-6和肿瘤坏死因子-α)以观察炎症过程。在OVX组、INF组和OVX+INF组中,与假手术组相比,BMD水平最低,骨钙素、骨桥蛋白、IL-1β、IL-6和TNF-α水平最高。与OVX组和OVX+INF对照组相比,ALA给药增加了BMD水平,降低了骨钙素、骨桥蛋白、IL-1β、IL-6和TNF-α水平。在老年性和绝经后骨质疏松症中,代表骨吸收的耦联平衡均被破坏。ALA对老年性和绝经后骨质疏松症均有保护作用。该药物在这些骨质疏松症模型中的积极作用可能源于其对骨转换标志物和细胞因子水平的积极影响。从这个角度来看,在深入研究结束时,ALA在临床上可能是老年性和绝经后类型骨质疏松症根治治疗的候选药物。