Taha Medhat, Elazab Sara T, Baokbah Tourki A S, Al-Kushi Abdullah G, Mahmoud Mohamed Ezzat, Abdelbagi Omer, Qusty Naeem F, El-Shenbaby Ibrahim, Babateen Omar, Badawy Alaa M, Ibrahim Mohie Mahmoud
Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Department of Anatomy, Al-Qunfudah Medical College, Umm Al-Qura University, Al-Qunfudah 28814, Saudi Arabia.
Toxics. 2023 Apr 16;11(4):377. doi: 10.3390/toxics11040377.
Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups ( = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly ( < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly ( < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway.
环孢素（CsA）因其免疫抑制作用，被认为是器官移植治疗方案的主要组成部分之一。然而，由于其肾毒性作用，其应用受到很大限制。扎姆扎姆水（ZW）是一种富含各种微量元素的碱性液体，具有很强的刺激抗氧化过程的能力。本研究旨在探讨ZW对环孢素A诱导的肾毒性的可能减轻作用及其潜在机制。40只大鼠被分为四组（每组n = 10）：对照组、ZW组、环孢素A组（皮下注射（SC）环孢素A（20 mg/kg/天））和环孢素A + 扎姆扎姆水组（皮下注射环孢素A并将ZW作为唯一饮用水（100 mL/笼/天），持续21天）。暴露于环孢素A显著（P < 0.001）增加了血清肌酐水平、脂质过氧化标志物水平（丙二醛；MDA）以及肾组织中凋亡标志物procaspase - 8、caspase - 8、caspase - 9、钙蛋白酶、细胞色素c、caspas - 3、P62和mTOR的表达。同时，它显著降低（P < 0.001）了自噬标志物（AMPK、ULK - I、ATag5、LC3和Beclin - 1）、抗凋亡蛋白Bcl - 2和抗氧化酶。此外，环孢素A的给药导致肾组织出现组织学改变。ZW显著（P < 0.001）逆转了环孢素A引起的所有变化，并最终在抑制环孢素A诱导的肾毒性方面取得了积极结果，表现为组织学结构的恢复、肾功能的改善、凋亡的抑制以及通过AMPK/mTOR途径增强自噬。
