Mangosteen Hinders Gamma Radiation-Mediated Oxidative Stress and Liver Injury by Down-Regulating TNF-α/NF-κB and Pro-Fibrotic Factor TGF-β1 Inducing Inflammatory Signaling

Abstract

Background: Liver injury due to ionizing radiation exposure either accidental or after radiotherapy treatment, may lead to many alterations in proteins expression related to inflammation or apoptosis. Our study investigated the curative effect of Mangosteen (MGS) extract (fruit rind) against ionizing radiation (IR) induced liver damage. Methods: Hepatotoxicity was induced in Wister rats by exposure to an acute single dose (6 Gy) of IR while MGS was given orally to rats (500 mg/kg bwt) and administered daily for 30 days after irradiation. Results: MGS treatment has significantly attenuated redox imbalance state and toxicity induced by protracted exposure to gamma-rays in liver tissues, which was substantiated by the significant amelioration of liver function tests, MDA contents, antioxidant enzymes (SOD and CAT) activities and NO level. MGS inhibited also the inflammatory markers (TNF-alpha, IL-6 and CRP) and downregulated transcriptional factor NF-Kappa-B/TGF-β1. These alterations were concomitant with an improvement of the Proliferating cell nuclear antigen (PCNA) which is a protein expressed in the nuclei of cells during cell cycle and is important for both DNA synthesis and DNA repair. These results were confirmed by amelioration in histological and ultrastructural examinations. Conclusion: We concluded that MGS could ameliorate via minimizing significantly the amount of oxidative damage, inflammations disturbances and pro-apoptotic alternations induced by IR. MGS may be a promising supplement with protective effects from irradiation-induced injury such as TNF-α/NF-κB/TGF-β1 management.

The metabolic and molecular mechanisms of α‑mangostin in cardiometabolic disorders (Review)

“…The ability of G. mangostana peel to improve liver morphology has also been reported by Hassan et al (70), John et al (12), Yan et al (71), and Fu et al (72) in various hepatic disease models. The improvement in hepatic structure has been associated with improved liver function tests indicated by reduced levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (70,72,73). The reduction in liver fibrosis has also been observed following treatment with G. mangostana peel (12,73).…”

“…The infusion of G. mangostana peel decreases hepatic structural damage induced by hydrogen peroxide (H 2 O 2 ) (69). The ability of G. mangostana peel to improve liver morphology has also been reported by Hassan et al (70), John et al (12), Yan et al (71), and Fu et al (72) in various hepatic disease models. The improvement in hepatic structure has been associated with improved liver function tests indicated by reduced levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (70,72,73).…”

“…cRP reduction was also observed, along with the reduced infiltration of inflammatory cells in liver and heart tissues of obese rats treated with G. mangostana pericarp rich in α-mangostin (12). In the study by Hassan et al (70), α-mangostin reduced IL-6 and TNF-α levels in liver tissues, reduced cRP, and inhibited NF-κB/TGF-β1 signaling in Wistar rats exposed to γ-irradiation.…”

“…Thioacetamide-and radiation-induced liver damage, as measured by ALT, AST and ALP liver biomarkers, has been also reported to be reversed in α-mangostin-treated mice (70,73). Hassan et al (70) previously exposed rats to ionizing radiation, in order to mimic the situations in which the liver is damaged due to radiotherapy treatment or accidental exposure. Radiation caused alterations in liver protein homeostasis and increased plasma liver markers like ALT, AST and ALP, indicating liver damage.…”

Modulation of endoplasmic reticulum stress via sulforaphane-mediated AMPK upregulation against nonalcoholic fatty liver disease in rats

“…This is in line with our findings in which significant increases in the oxidative stress markers such as MDA were accompanied by decreased activities of catalase, SOD, and GSH content in the HFD and HFD + IR groups compared to the control group, suggesting the presence of oxidative stress that may play an essential role in the insulin resistance in the HFD and HFD + IR groups. In this context, the significant increase in liver MDA could be due to the interaction of ionizing radiation with water, which produces a variety of reactive oxygen species (ROS), including hydroxyl radical (•OH), hydrogen peroxide (H2O2), superoxide radical (•O 2 ), and subsequently oxygen (O 2 ) as an attack on the fatty acid composition of membrane lipids (Hassan et al 2021 ). Nevertheless, SFN treatment reduced the oxidative stress in rats fed on HFD and/or exposed to an IR, as detected by the activation of key enzymes involved in the balance of the redox state, such as catalase, SOD, and GSH.…”