Tyrosol ameliorates Urografin induced acute hepatorenal toxicity via Nrf2 and HO1 pathways based on biochemical and histopathological evaluations

The clinical use of iodinated radiocontrast agents (especially Urografin) can lead to contrast-induced nephropathy (CIN) and hepatotoxicity mediated by oxidative stress and inflammation. This study aimed to investigate the protective potential of Tyrosol, a major bioactive component of virgin olive oil, against Urografin-induced acute hepato-renal toxicity. Thirty-two female Wistar albino rats were randomly assigned to four groups ( n = 8). To evaluate the protective efficacy of Tyrosol against contrast-induced toxicity, a 30-day pretreatment model was established. Rats in the treatment cohorts received Tyrosol (20 mg/kg/day) via oral gavage for 30 consecutive days, followed by a single intravenous (IV) injection of Urografin (6 mL/kg) via the tail vein on the 30th day. At 48 h post-injection, serum hepatorenal function markers (urea, creatinine, ALT, AST, ALP, albumin, Ca²⁺, and inorganic phosphorus) were measured photometrically. Furthermore, liver and kidney tissues were evaluated for oxidative stress indicators (MDA, GSH, GPx, CAT via spectrophotometrically) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 via ELISA). For molecular assessments, Nrf-2 and HO-1 protein expressions in kidney tissues were quantified via Western blotting. Finally, liver and kidney sections were stained with hematoxylin and eosin for histopathological evaluation. Urografin administration significantly elevated serum urea, creatinine, and AST levels while decreasing ALP. It induced marked oxidative stress in both liver and kidney tissues by elevating MDA levels and depleting GSH levels and GPx activities, alongside triggering a cytokine storm characterized by increased TNF-α, IL-1β, and IL-6 levels. Tyrosol pretreatment successfully restored serum urea, renal MDA, and hepatic/renal GSH to control levels, and completely normalized TNF-α and IL-1β concentrations. However, the restorations of creatinine, AST, IL-6, and hepatic MDA were partial and did not reach control baseline values. Molecular analyses demonstrated that Urografin suppressed the cellular defense mechanisms, whereas Tyrosol reactivated the Nrf-2/HO-1 signaling pathway by significantly elevating their protein expressions. Histopathologically, Tyrosol significantly ameliorated Urografin-induced hepatic inflammatory infiltration, as well as renal hemorrhage, mononuclear cell infiltration, and hydropic degeneration. Tyrosol (20 mg/kg) provides robust multi-organ protection against Urografin-induced acute hepato-renal injury in a female rat model by intensely reactivating the Nrf-2/HO-1 antioxidant pathway and suppressing the pro-inflammatory cascade.