Abdelmissih Sherine, Ahmed Rashed Laila, Sharif Ismail Negm Mohamed, Mohamed Sayed Walaa, Mahmoud Hesham M, Elmorsy Soha
Department of Medical Pharmacology, Faculty of Medicine Kasr Al-Ainy, Cairo University, Cairo, EGY.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Kasr Al-Ainy, Cairo University, Cairo, EGY.
Cureus. 2025 Mar 12;17(3):e80486. doi: 10.7759/cureus.80486. eCollection 2025 Mar.
The presumed implication of thromboembolic and oxidative stress pathways in parkinsonism guided the current research toward the exploration of the anticoagulant dabigatran etexilate (DE) as a thrombin inhibitor in the cobalt chloride (CoCl)-induced parkinsonism (CIP) model, a model of significance to industrial toxins-related health issues.
Oral CoCl (12.5 mg/kg) was administered daily for 60 days, with the introduction of benztropine mesylate (BM) (10 mg/kg) and/or DE (3 mg/kg) on day 31. Rearing, postural instability, and pasta handling were evaluated, followed by histopathologic examination of the substantia nigra (SN) and striatum (STR). The expressions of brain dopamine receptor 2 ( ), adenosinereceptor 1 (A) and 2A (A), and protease-activated receptor 1 (PAR1), as well as the brain levels of dopamine (DA), endothelin 1 (ET1), malondialdehyde (MDA), and glutathione (GSH), were assessed.
BM+DE restored the number of rears to the control level, compared to being reduced in the CIP model. BM+DE restored the first, second, third, and average displacement distances to the control level, compared to being reduced in the CIP model. BM+DE was superior to either BM or DE in restoring the time to finish eating pasta and the number of adjustments of forepaws while eating to control levels after being affected in the CIP model. BM+DE restored DA to the control level and was superior to DE in restoring D to the control level. BM+DE was superior to BM in restoring Aand A increasing A/Abeyond the control levelBM+DE was superior to BM in restoring PAR1 and ET1 to control levels. BM+DE was superior to BM in restoring MDA to the control level and was superior to both BM and DE in increasing GSH beyond the control level. BM+DE exhibited the highest percentage of preserved neurons in SN, which was negatively correlated with MDA.
BM+DE offers a therapeutic potential for parkinsonism triggered by chronic exposure to CoCl. The implication of thrombin-related factors and oxidative stress in the modulation of the dopaminergic-adenosinergic crosstalk is plausible.
血栓栓塞和氧化应激途径在帕金森症中的假定作用，引导了当前的研究朝着在氯化钴（CoCl）诱导的帕金森症（CIP）模型中探索抗凝血剂达比加群酯（DE）作为凝血酶抑制剂的方向发展，该模型对与工业毒素相关的健康问题具有重要意义。
每天口服CoCl（12.5毫克/千克），持续60天，在第31天引入甲磺酸苯扎托品（BM）（10毫克/千克）和/或DE（3毫克/千克）。评估竖毛、姿势不稳和面食处理情况，随后对黑质（SN）和纹状体（STR）进行组织病理学检查。评估脑多巴胺受体2（ ）、腺苷受体1（A）和2A（A）以及蛋白酶激活受体1（PAR1）的表达，以及脑内多巴胺（DA）、内皮素1（ET1）、丙二醛（MDA）和谷胱甘肽（GSH）的水平。
与CIP模型中减少的情况相比，BM + DE将竖毛次数恢复到了对照水平。与CIP模型中减少的情况相比，BM + DE将首次、第二次、第三次和平均位移距离恢复到了对照水平。在CIP模型中受到影响后，BM + DE在将吃完面食的时间和进食时前爪调整次数恢复到对照水平方面优于BM或DE。BM + DE将DA恢复到对照水平，在将D恢复到对照水平方面优于DE。BM + DE在恢复A和A以及使A/A超过对照水平方面优于BM。BM + DE在将PAR1和ET1恢复到对照水平方面优于BM。BM + DE在将MDA恢复到对照水平方面优于BM，在使GSH超过对照水平方面优于BM和DE。BM + DE在SN中显示出最高的神经元保留百分比，这与MDA呈负相关。
BM + DE对慢性暴露于CoCl引发的帕金森症具有治疗潜力。凝血酶相关因子和氧化应激在调节多巴胺能 - 腺苷能相互作用中的作用是合理的。
