<![CDATA[Iron overload can induce oxidative stress and kidney injury by increasing reactive oxygen species (ROS) production and reducing antioxidant capacity, including total glutathione (T-GSH). Chelation therapy using deferiprone (DFP) as a standard agent and ethanolic Phaleria macrocarpa (PM) fruit extract as a natural candidate is expected to reduce renal iron accumulation and restore redox balance. This study aimed to evaluate the effects of DFP, PM, and their combination on renal iron and T-GSH levels in an iron-overloaded rat model. A parallel in vivo experiment was conducted using 30 male Sprague-Dawley rats (29 analyzed) with iron overload induced by intraperitoneal iron-dextran injection (0.3 mL, ±15 mg Fe) twice weekly for three weeks, followed by daily oral treatments for five weeks. The rats were divided into six groups: normal (N), iron overload (IO), DFP 462.5 mg/kg BW (D), PM 100 mg/kg BW (PM), DFP 462.5 mg/kg BW + PM (DPM-1), and DFP 231.25 mg/kg BW + PM (DPM-2). Kidney iron levels were determined using atomic absorption spectrophotometry (AAS, λ 248.3 nm), and T-GSH was measured colorimetrically (λ 412 nm). Statistical analysis employed one-way ANOVA with post-hoc LSD for iron data and the Mann-Whitney U test for T-GSH (p < 0.05). The IO group showed a 1.44-fold increase in kidney iron compared with the normal group, while DFP, PM, and their combinations had no significant effect (p = 0.490). Mann-Whitney analysis revealed a significant difference in T-GSH between PM and DPM-1 (p = 0.034). In conclusion, the DFP-PM combination (DPM-1) demonstrated a potential synergistic effect in enhancing renal T-GSH levels, although it did not significantly reduce iron accumulation. Further studies with longer treatment durations and additional antioxidant parameters are recommended to confirm the protective potential of DFP-PM combination therapy against oxidative stress and ferroptosis in iron-overloaded kidneys.]]>
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