Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabuk University, Tabuk, Kingdom of Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Jun;391(6):603-612. doi: 10.1007/s00210-018-1489-1. Epub 2018 Mar 29.
Stroke is a lethal disease, but it disables more than it kills. Stroke is the second leading cause of death and the most frequent cause of permanent disability in adults worldwide, with 90% of survivors having residual deficits. The pathophysiology of stroke is complex and involves a strong inflammatory response associated with oxidative stress and activation of several proteolytic enzymes. The current study was designed to investigate the effect of arginase inhibitors (L-citruline and L-ornithine) against ischemic stroke induced in rats by middle cerebral artery occlusion (MCAO). MCAO resulted in alteration in rat behavior, brain infarct, and edema associated with disruption of the blood-brain barrier (BBB). This was mediated through overexpression of arginase I and II, inducible NOS (iNOS), malondialdehyde (MDA), advanced glycation end products (AGEs), TNF-α, and IL-1β and downregulation of endothelial nitric oxide synthase (eNOS). Treatment with L-citruline and L-ornithine and the standard neuroprotective drug cerebrolysin ameliorated all the deleterious effects of stroke. These results indicate the possible use of arginase inhibitors in the treatment of stroke after suitable clinical trials are done.
中风是一种致命的疾病，但它造成的残疾比死亡更常见。中风是全球范围内第二大致死原因和成年人中最常见的永久性残疾原因，90%的幸存者都有残留缺陷。中风的病理生理学很复杂，涉及到强烈的炎症反应，与氧化应激和几种蛋白水解酶的激活有关。本研究旨在探讨精氨酸酶抑制剂（L-瓜氨酸和 L-鸟氨酸）对大脑中动脉闭塞（MCAO）诱导的大鼠缺血性中风的影响。MCAO 导致大鼠行为改变、脑梗死和脑水肿，同时血脑屏障（BBB）被破坏。这是通过精氨酸酶 I 和 II、诱导型一氧化氮合酶（iNOS）、丙二醛（MDA）、晚期糖基化终产物（AGEs）、TNF-α 和 IL-1β 的过度表达以及内皮型一氧化氮合酶（eNOS）的下调来介导的。用 L-瓜氨酸和 L-鸟氨酸以及标准神经保护药物脑活素治疗可改善中风的所有有害影响。这些结果表明，在进行适当的临床试验后，精氨酸酶抑制剂可能用于中风的治疗。
