University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Int J Toxicol. 2010 May-Jun;29(3):318-25. doi: 10.1177/1091581810365568.
Cyclosporine A is a well-known immunosuppressant drug that is currently used for prevention of allograft rejection. The current study was conducted to explore the therapeutic potential of cyclosporine A against 3-nitropropionic acid (3-NP)-induced neurotoxicity, an animal model of Huntington disease (HD). Systemic administration of 3-NP (10 mg/kg) for 14 days significantly impaired body weight, motor activity, biochemical parameters (raised lipid peroxidation, nitrite concentration, depletion of superoxide dismutase [SOD] and catalase), and mitochondrial enzymes. Cyclosporine A (2.5, 5, and 10 mg/kg) treatment significantly attenuated behavioral, biochemical, and cellular alterations. Furthermore, L-arginine pretreatment with cyclosporine A (5 mg/kg) significantly reversed the protective effect of cyclosporine A. However, L-nitro-arginine methyl ester (L-NAME; 10 mg/kg) pretreatment potentiated the protective effect of cyclosporine A (5 mg/kg). Study highlights the therapeutic potential of cyclosporine A in the treatment of HP. Study suggests that nitric oxide (NO) modulation is involved in the neuroprotective effect of cyclosporine A against 3-NP neurotoxicity.
环孢素 A 是一种众所周知的免疫抑制剂药物，目前用于预防同种异体移植排斥。本研究旨在探讨环孢素 A 对 3-硝基丙酸（3-NP）诱导的神经毒性（亨廷顿病（HD）的动物模型）的治疗潜力。3-NP（10mg/kg）连续 14 天全身给药显著损害体重、运动活性、生化参数（脂质过氧化、亚硝酸盐浓度升高，超氧化物歧化酶[SOD]和过氧化氢酶耗竭）和线粒体酶。环孢素 A（2.5、5 和 10mg/kg）治疗显著减轻了行为、生化和细胞改变。此外，环孢素 A（5mg/kg）预处理 L-精氨酸显著逆转了环孢素 A 的保护作用。然而，L-硝基精氨酸甲酯（L-NAME；10mg/kg）预处理增强了环孢素 A（5mg/kg）的保护作用。研究强调了环孢素 A 在治疗亨廷顿病中的治疗潜力。研究表明，一氧化氮（NO）调节参与了环孢素 A 对 3-NP 神经毒性的神经保护作用。
