Department of Pharmacology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Department of Microbiology and Immunology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Jordana 19, 41-808 Zabrze, Poland.
Int J Mol Sci. 2023 May 19;24(10):8991. doi: 10.3390/ijms24108991.
The extension of human life makes it more and more important to prevent and treat diseases of the elderly, including Alzheimer's disease (AD) and osteoporosis. Little is known about the effects of drugs used in the treatment of AD on the musculoskeletal system. The aim of the present study was to investigate the effects of donepezil, an acetylcholinesterase inhibitor, on the musculoskeletal system in rats with normal and reduced estrogen levels. The study was carried out on four groups of mature female rats: non-ovariectomized (NOVX) control rats, NOVX rats treated with donepezil, ovariectomized (OVX) control rats and OVX rats treated with donepezil. Donepezil (1 mg/kg p.o.) was administered for four weeks, starting one week after the ovariectomy. The serum concentrations of CTX-I, osteocalcin and other biochemical parameters, bone mass, density, mineralization, histomorphometric parameters and mechanical properties, and skeletal muscle mass and strength were examined. Estrogen deficiency increased bone resorption and formation and worsened cancellous bone mechanical properties and histomorphometric parameters. In NOVX rats, donepezil decreased bone volume to tissue volume ratio in the distal femoral metaphysis, increased the serum phosphorus concentration and tended to decrease skeletal muscle strength. No significant bone effects of donepezil were observed in OVX rats. The results of the present study indicate slightly unfavorable effects of donepezil on the musculoskeletal system in rats with normal estrogen levels.
人类寿命的延长使得预防和治疗老年人疾病变得越来越重要，包括阿尔茨海默病（AD）和骨质疏松症。目前对于用于治疗 AD 的药物对骨骼肌肉系统的影响知之甚少。本研究旨在研究乙酰胆碱酯酶抑制剂多奈哌齐对正常和雌激素水平降低的大鼠骨骼肌肉系统的影响。该研究在四组成熟雌性大鼠中进行：未去卵巢（NOVX）对照大鼠、去卵巢后给予多奈哌齐的 NOVX 大鼠、去卵巢对照（OVX）大鼠和去卵巢后给予多奈哌齐的 OVX 大鼠。多奈哌齐（1 mg/kg p.o.）给药 4 周，在去卵巢后 1 周开始给药。检测血清 CTX-I、骨钙素和其他生化参数、骨量、密度、矿化、组织形态计量学参数和机械性能以及骨骼肌质量和力量。雌激素缺乏增加了骨吸收和形成，并使松质骨机械性能和组织形态计量学参数恶化。在 NOVX 大鼠中，多奈哌齐降低了股骨远端干骺端的骨体积与组织体积比，增加了血清磷浓度，并倾向于降低骨骼肌力量。在 OVX 大鼠中，多奈哌齐对骨骼肌肉系统没有明显的影响。本研究结果表明，在雌激素水平正常的大鼠中，多奈哌齐对骨骼肌肉系统有轻微的不利影响。
