Radioprotective Effects of Carvacrol and/or Thymol against Gamma Irradiation-Induced Acute Nephropathy: In Silico and In Vivo Evidence of the Involvement of Insulin-like Growth Factor-1 (IGF-1) and Calcitonin Gene-Related Peptide

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.