Akila Asmaa A, Gad Rania A, Ewees Mohamed Gamal El-Din, Abdul-Hamid Manal, Abdel-Reheim Eman S
Molecular Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, 62511, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, 62511, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar;398(3):2609-2625. doi: 10.1007/s00210-024-03380-5. Epub 2024 Sep 5.
Gentamicin (Genta)-induced nephrotoxicity poses a significant clinical challenge due to its detrimental effects on kidney function. Clopidogrel (Clop), an antiplatelet drug known for its ability to prevent blood clots by inhibiting platelet aggregation, also has potential effects on oxidative stress and cell death. This study investigates Clop's protective role against Genta-induced nephrotoxicity, emphasizing the importance of the coagulation cascade. The 32 adult male albino rats were randomly assigned to four groups of eight (n = 8). The first group received only the vehicle. Genta was injected intraperitoneally at 100 mg/kg/day for 8 days in the second group. Groups 3 and 4 received oral Clop at 10 and 20 mg/kg/day for 1 week before Genta delivery and throughout the experiment. Renal tissue showed renal function tests, oxidative stress, pro-inflammatory cytokines, apoptotic markers, coagulation profile, and fibrin expression. Clop improved Genta-induced kidney function and histopathology. Clop substantially reduced pro-inflammatory cytokines, oxidative stress indicators, pro-apoptotic proteins, and fibrin protein. Clop also significantly boosted renal tissue anti-inflammatory and anti-apoptotic protein expression. Genta-induced nephrotoxicity involves oxidative stress, apoptosis, and coagulation system activation, according to studies. This study underscores that Genta-induced nephrotoxicity is associated with oxidative stress, apoptosis, and activation of the coagulation system. Clop's protective effects on nephrons are attributed to its anticoagulant, antioxidant, anti-inflammatory, and anti-apoptotic properties, presenting it as a promising therapeutic strategy against Genta-induced kidney damage.
庆大霉素（Genta）诱导的肾毒性因其对肾功能的有害影响而构成重大临床挑战。氯吡格雷（Clop）是一种抗血小板药物，以通过抑制血小板聚集来预防血栓形成而闻名，它对氧化应激和细胞死亡也有潜在影响。本研究调查了Clop对Genta诱导的肾毒性的保护作用，强调了凝血级联反应的重要性。32只成年雄性白化大鼠被随机分为四组，每组8只（n = 8）。第一组仅接受赋形剂。第二组腹腔注射Genta，剂量为100 mg/kg/天，持续8天。第三组和第四组在给予Genta前1周及整个实验过程中，每天口服10和20 mg/kg的Clop。对肾组织进行肾功能测试、氧化应激、促炎细胞因子、凋亡标志物、凝血指标和纤维蛋白表达检测。Clop改善了Genta诱导的肾功能和组织病理学。Clop显著降低了促炎细胞因子、氧化应激指标、促凋亡蛋白和纤维蛋白。Clop还显著提高了肾组织抗炎和抗凋亡蛋白的表达。研究表明，Genta诱导的肾毒性涉及氧化应激、细胞凋亡和凝血系统激活。本研究强调，Genta诱导的肾毒性与氧化应激、细胞凋亡和凝血系统激活有关。Clop对肾单位的保护作用归因于其抗凝、抗氧化、抗炎和抗凋亡特性，使其成为对抗Genta诱导的肾损伤的一种有前景的治疗策略。
