Syringic acid pretreatment potentiates antioxidant mechanism and downregulates inflammatory signaling towards doxorubicin-related oxidoinflammatory hepatorenal damage in rats

Although doxorubicin (DOX) is a first-line antineoplastic drug, its clinical use is limited due to its widespread side effects. Hepatic and renal metabolic clearance causes DOX accumulation in these organ systems, ultimately leading to oxidative-inflammatory damage. This study investigated the potential impact of syringic acid (SA), a natural antioxidant phenolic compound, against in vivo DOX-evoked hepatorenal damage. SA was orally administered to rats at 100 mg/kg body weight for 10 consecutive days. On the 8th day of the study, DOX was administered at 20 mg/kg by single-dose intraperitoneal injection to prompt hepatorenal toxicity. Hepatorenal toxicity was assessed by measuring serum alanine transferase (ALT), aspartate transferase (AST), blood urea nitrogen (BUN), and creatinine (Cre). Histopathological evaluation of kidney and liver tissues was also performed to observe DOX-related damage. The concentrations of malondialdehyde (MDA) and glutathione (GSH), along with the activities of catalase (CAT) and superoxide dismutase (SOD), were measured in the hepatorenal tissues, in addition to the concentration of 8-OHdG in serum, to determine the protective effect of SA against oxidative stress. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were investigated with molecular and immunohistochemical analysis in hepatorenal tissues, evaluating the inflammation. SA treatment prevented DOX-aberrant elevation of hepatorenal biomarkers in serum, besides histopathological alterations in rats’ liver and kidney. Additionally, SA markedly counteracted DOX-provoked oxidative damage as evidenced by outstanding reduction in lipid peroxidation and 8-OHdG, conjointly promoted GSH contents, and amelioration of activities of SOD and CAT. Similarly, SA-treated rats exhibited attenuation of hepatorenal inflammation via diminished TNF-α and IL-6 levels. SA exerted a hepatorenal protective effect in rats by exhibiting antioxidant and anti-inflammatory activities. © The Author(s) 2026.