Mahran Yasmen F, Al-Kharashi Layla A, Atawia Reem T, Alanazi Rawan Turki, Dhahi Amal M Bin, Alsubaie Rawd, Badr Amira M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11211, Saudi Arabia.
Biomedicines. 2023 Sep 13;11(9):2521. doi: 10.3390/biomedicines11092521.
Radiotherapy (RT) is an effective curative cancer treatment. However, RT can seriously damage kidney tissues resulting in radiotherapy nephropathy (RN) where oxidative stress, inflammation, and apoptosis are among the common pathomechanisms. Carvacrol and thymol are known for their antioxidative, anti-inflammatory, and radioprotective activities. Therefore, this study investigated the nephroprotective potentials of carvacrol and/or thymol against gamma (γ) irradiation-induced nephrotoxicity in rats along with the nephroprotection mechanisms, particularly the involvement of insulin-like growth factor-1 (IGF-1) and calcitonin gene-related peptide (CGRP). Methods: Male rats were injected with carvacrol and/or thymol (80 and 50 mg/kg BW in the vehicle, respectively) for five days and exposed to a single dose of irradiation (6 Gy). Then, nephrotoxicity indices, oxidative stress, inflammatory, apoptotic biomarkers, and the histopathological examination were assessed. Also, IGF-1 and CGRP renal expressions were measured. Results: Carvacrol and/or thymol protected kidneys against γ-irradiation-induced acute RN which might be attributed to their antioxidative, anti-inflammatory, and antiapoptotic activities. Moreover, both reserved the γ -irradiation-induced downregulation of CGRP- TNF-α loop in acute RN that might be involved in the pathomechanisms of acute RN. Additionally, in Silico molecular docking simulation of carvacrol and thymol demonstrated promising fitting and binding with CGRP, IGF-1, TNF-α and NF-κB through the formation of hydrogen, hydrophobic and alkyl bonds with binding sites of target proteins which supports the reno-protective properties of carvacrol and thymol. Collectively, our findings open a new avenue for using carvacrol and/or thymol to improve the therapeutic index of γ-irradiation.
放射疗法（RT）是一种有效的癌症治疗方法。然而，放射疗法会严重损害肾脏组织，导致放射性肾病（RN），氧化应激、炎症和细胞凋亡是常见的发病机制。香芹酚和百里酚以其抗氧化、抗炎和辐射防护活性而闻名。因此，本研究调查了香芹酚和/或百里酚对大鼠γ射线照射诱导的肾毒性的肾保护潜力以及肾保护机制，特别是胰岛素样生长因子-1（IGF-1）和降钙素基因相关肽（CGRP）的参与情况。方法：雄性大鼠分别注射香芹酚和/或百里酚（分别以80和50mg/kg体重溶于溶剂中），持续五天，然后接受单次照射（6Gy）。随后，评估肾毒性指标、氧化应激、炎症、凋亡生物标志物以及组织病理学检查。此外，还测量了IGF-1和CGRP在肾脏中的表达。结果：香芹酚和/或百里酚保护肾脏免受γ射线照射诱导的急性放射性肾病，这可能归因于它们的抗氧化、抗炎和抗凋亡活性。此外，两者都保留了γ射线照射诱导的急性放射性肾病中CGRP - TNF-α环的下调，这可能参与急性放射性肾病的发病机制。此外，香芹酚和百里酚的计算机模拟分子对接模拟显示，通过与靶蛋白结合位点形成氢键、疏水键和烷基键，它们与CGRP、IGF-1、TNF-α和NF-κB有良好的拟合和结合，这支持了香芹酚和百里酚的肾保护特性。总的来说，我们的研究结果为使用香芹酚和/或百里酚提高γ射线照射的治疗指数开辟了一条新途径。
