Effects of methylphenidate on femoral bone growth in male rats.

Gökçe Nur Say, Mehmet Emin Önger, Ferhat Say, Onur Yontar, Oktay Yapıcı
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Abstract

The use of Methylphenidate (MP) can have adverse effects on bone growth and mineralization. This study aimed to investigate the underlying pathophysiology of MP-induced skeletal deficits in growing rats using stereological and immunohistochemical methods. Male rats, aged 4 weeks, were orally treated with MP through an 8-h/day water drinking protocol. The rats (n=30) were randomly divided into three groups: MP-High Dose (30/60 mg/kg/day MP), MP-Low Dose (4/10 mg/kg/day MP), and control (water only). After 13 weeks, the femoral bones were assessed using calliper measurements, dual-energy X-ray absorptiometry, and biomechanical evaluation. The total femur volume, cartilage volume, growth zone volume, and volume fractions were determined using the Cavalieri method. Immunohistochemical analyses were conducted using alkaline phosphatase and anti-calpain antibody staining. Rats exposed to MP exhibited significant reductions in weight gain, femoral growth, bone mineralization, and biomechanical integrity compared to the control group. The total femoral volume of MP-treated rats was significantly lower than that of the control group. The MP-High Dose group showed significantly higher ratios of total cartilage volume/total femoral volume and total growth zone volume/total femoral volume than the other groups. Immunohistochemical evaluation of the growth plate revealed reduced osteoblastic activity and decreased intracellular calcium deposition with chronic MP exposure. The possible mechanism of MP-induced skeletal growth retardation may involve the inhibition of intracellular calcium deposition in chondrocytes of the hypertrophic zone in the growth plate. In this way, MP may hinder the differentiation of cartilage tissue from bone tissue, resulting in reduced bone growth and mineralization.

哌甲酯对雄性大鼠股骨生长的影响。
哌甲酯(MP)的使用可能对骨骼生长和矿化产生不利影响。本研究旨在使用体视学和免疫组织化学方法研究生长中大鼠MP诱导的骨骼缺陷的潜在病理生理学。雄性大鼠,4周龄,通过8小时/天的饮水方案口服MP。将大鼠(n=30)随机分为三组:MP高剂量组(30/60 mg/kg/天MP)、MP低剂量组(4/10 mg/kg/天AMP)和对照组(仅水)。13周后,使用卡尺测量、双能X射线吸收仪和生物力学评估对股骨进行评估。使用Cavalieri方法测定股骨总体积、软骨体积、生长区体积和体积分数。使用碱性磷酸酶和抗钙蛋白酶抗体染色进行免疫组织化学分析。与对照组相比,暴露于MP的大鼠体重增加、股骨生长、骨矿化和生物力学完整性显著降低。MP处理大鼠的股骨总体积显著低于对照组。MP高剂量组的软骨总体积/股骨总体积和生长区总体积/股骨头总体积的比值明显高于其他组。生长板的免疫组织化学评估显示,慢性MP暴露后,成骨细胞活性降低,细胞内钙沉积减少。MP诱导的骨骼生长迟缓的可能机制可能涉及抑制生长板中肥大区软骨细胞中的细胞内钙沉积。这样,MP可能阻碍软骨组织与骨组织的分化,导致骨生长和矿化减少。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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