Impact of Washingtonia robusta Leaves on Gamma Irradiation-Induced Hepatotoxicity in Rats and Correlation with STING Pathway and Phenolic Composition

Abstract

Exposure to ionizing radiation usually results in cellular oxidative damage and may induce liver toxicity. The efficiency of the ethanol extracts of Washingtonia filifera (EWF) and Washingtonia robusta (EWR) leaves in alleviating γ-radiation-induced oxidative hepatotoxicity was herein explored. Proximate and macronutrient composition of the leaves was determined to establish reliable quality control criteria. Colorimetric estimation of total phenolic (TPC) and flavonoid (TFC) contents revealed their occurrence in larger amounts in EWR. In vitro evaluation of the antioxidant capacity by 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays confirmed higher efficiency of EWR designating a close correlation with phenolic composition. Four phenolics, viz., naringenin, kaempferol, quercetin, and gallic acid, were isolated from EWR. In vivo assessment of the extracts’ antioxidant potential was performed on γ-irradiated (7.5 Gy) female rats. EWR was found more efficient in restoring the elevated liver index, ALT, albumin, cholesterol, and reactive oxygen species (ROS) levels. Both extracts ameliorated the increase in the stimulator of interferon gene (STING) expression. Bioactivity was confirmed by immuno-histochemical examination of inflammatory and apoptotic biomarkers (TNF-α, IL-6 and caspase-3) and histopathological architecture. In addition, the interactions of the isolated compounds with STING were assessed in silico by molecular docking. Therefore, Washingtonia robusta leaves might be suggested as a valuable nutritional supplement to alleviate radiotherapy-induced hepatotoxicity.

Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

“…Ionizing radiation is established to induce oxidative stress through the generation of ROS, resulting in an imbalance in the pro-oxidant/antioxidant status of the cells, [51][52][53] which in sequence leads to lipid peroxidation and increases MDA levels. 54,55 Similar to a previous report by Chen et al, Nrf2 expression levels were increased in response to ionizing radiation, confirming the critical role of this nuclear factor in the antioxidant cell response.…”

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition

“…76 This may account for the high level of ROS in tumor tissues, which in turn react with the polyunsaturated fatty acids of lipid membranes and induces lipid peroxidation. 73,77 These outcomes reflect the apoptotic and killing effect of BL together with inhibiting Ki-67 and PARP-1, which give BL the opportunity to act as a significant radiosensitizer.…”

Review of Phyto-Medical Extracts’ and Compounds’ Anti-Radiation Properties

“…In addition, liver biomarkers such as ALT, cholesterol, and triglycerides showed a significant decrease (p≤0.05) after treatment, approaching normal levels. Treatment also led to a reduction in the expression of the STING gene [57].…”