Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt.
Eur J Pharmacol. 2018 Apr 5;824:148-156. doi: 10.1016/j.ejphar.2018.02.001. Epub 2018 Feb 13.
Chronic alcoholism is a risk factor for kidney injury. Clonidine is an α-adrenergic receptor/imidazoline-1 receptor agonist that can reduce blood pressure and maintain renal functions. This study aims to investigate the possible ameliorative effects of clonidine on ethanol induced kidney injury and its mechanism of action. Kidney injury was induced in rats by adding ethanol to drinking water for eight weeks. Clonidine effects on kidney functions and histopathology were measured. Moreover, phentolamine (α-adrenergic receptor antagonist), efaroxan (imidazoline-1 receptor antagonist) and rilmenidine (imidazoline-1 receptor agonist) were used to clarify the role of imidazoline-1 receptor in mediating renal ameliorative effects. Also, the effect of clonidine on liver functions and metabolic changes, in addition to renal oxidative stress, inflammatory and apoptotic pathways were measured. Results showed that, clonidine improved renal functions and reduced ethanol induced renal inflammation and fibrosis. On the other hand, efaroxan, only, blocked clonidine effects on kidney functions. Rilmenidine decreased kidney injury like clonidine. Both clonidine and rilmenidine increased renal nischarin gene expression. Furthermore, clonidine improved liver functions, increased serum insulin and decreased serum advanced glycation end products (metabolic markers). Also, clonidine reduced renal oxidative stress as reflected by decreased myeloperoxidase, malondialdehyde, inducible nitric oxide synthase and total nitric oxide levels and increased superoxide dismutase level. Moreover, clonidine reduced renal tumor necrosis factor-α (inflammatory marker) and caspase-3 (apoptotic marker) levels, while increased renal prostaglandine E2 and interleukin-10 levels (anti-inflammatory markers). In conclusion, clonidine can reduce ethanol induced kidney injury, at least in part, by stimulating imidazoline-1 receptor signaling.
慢性酒精中毒是肾脏损伤的一个风险因素。可乐定是一种α-肾上腺素能受体/咪唑啉-1 受体激动剂，可降低血压并维持肾功能。本研究旨在探讨可乐定对乙醇诱导的肾脏损伤的可能改善作用及其作用机制。通过在饮用水中添加乙醇，在大鼠中诱导肾脏损伤 8 周。测量可乐定对肾功能和组织病理学的影响。此外，还使用酚妥拉明（α-肾上腺素能受体拮抗剂）、efaroxan（咪唑啉-1 受体拮抗剂）和利美尼定（咪唑啉-1 受体激动剂）来阐明咪唑啉-1 受体在介导肾脏改善作用中的作用。还测量了可乐定对肝功能和代谢变化以及肾脏氧化应激、炎症和凋亡途径的影响。结果表明，可乐定改善了肾功能，减轻了乙醇引起的肾脏炎症和纤维化。另一方面，只有 efaroxan 阻断了可乐定对肾功能的作用。利美尼定像可乐定一样降低了肾脏损伤。可乐定和利美尼定都增加了肾脏 nischarin 基因的表达。此外，可乐定改善了肝功能，增加了血清胰岛素，降低了血清晚期糖基化终产物（代谢标志物）。可乐定还降低了肾脏氧化应激，表现为髓过氧化物酶、丙二醛、诱导型一氧化氮合酶和总一氧化氮水平降低，超氧化物歧化酶水平升高。此外，可乐定降低了肾脏肿瘤坏死因子-α（炎症标志物）和 caspase-3（凋亡标志物）水平，同时增加了肾脏前列腺素 E2 和白细胞介素-10 水平（抗炎标志物）。总之，可乐定通过刺激咪唑啉-1 受体信号至少部分减轻了乙醇引起的肾脏损伤。
