Hepatosplenic protective role of quercetin in gamma-irradiated rats: modulation of oxidative stress, inflammatory and TGF-β signaling pathways
摘要
This study evaluates quercetin’s ability to prevent liver and spleen disorders caused by gamma radiation in an experimental rat model and investigates the potential mechanism.
MethodsFour sets of eight rats were randomly selected. Group I served as a negative control, and Group II received a single dose of γ-radiation (7 Gy). Group III was given 200 mg/kg of quercetin daily for ten days. Group IV: Rats were pretreated with quercetin for ten days; on the seventh day of quercetin treatment, the animals were subjected to a single dose of γ-radiation (7 Gy). AST, ALT, albumin and total protein levels are measured in serum as well as oxidative biomarkers contents (ROS and GSH) are estimated in liver and spleen tissues.IL-6 and TGF-β protein expression are quantified immunohistochemically in addition to histopathological examination of liver and spleen tissues of rats.
ResultsThe liver and spleen tissues of irradiated rats have lower amounts of GSH and higher levels of reactive oxygen species (ROS) as compared to the control. Additionally, there was an increase in serum alanine transaminase (ALT) and aspartate aminotransferase (AST) and upregulation of transforming growth factor beta (TGF-β) and interleukin-6 (IL-6) expression, while serum albumin and total protein concentrations decreased. Conversely, oral quercetin pretreatment significantly improved indicators of liver function. Histopathological architecture and immunohistochemical analysis of fibrogenic and inflammatory biomarkers (IL-6 and TGF-β) validated the bioactivity of the flavonoid. By controlling IL-6 and TGF-β expression, quercetin reduced radiotherapy-induced liver damage, possibly via mitigating liver oxidative stress, inflammation, and fibrosis.
ConclusionTo reduce the hepatic and splenic toxicity caused by radiation therapy, quercetin may be administered as a safe, stand-alone radioprotective medication.
Graphical Abstract