Protective effects of medicinal honey against doxorubicin-induced hepatorenal toxicity in rats: A novel grading index (PAD score) based on phenolic content and antioxidant capacity

Background: Doxorubicin is an effective anticancer drug whose clinical use is limited by oxidative liver and kidney toxicity. High-PAD-score honey, a novel index reflecting honey quality and bioactive potential, is rich in phenolic compounds and antioxidants and may mitigate these toxic effects. This study aimed to evaluate the protective effects of PAD-classified honey against doxorubicin-induced hepatorenal toxicity in rats. Methods: Fifteen honey samples collected from different regions of Iran were biochemically characterized using a novel PAD scoring system calculated as the sum of four parameters: total phenolic content, antioxidant capacity, protein concentration, and diastase activity. Based on their PAD values, honeys were classified into high-, moderate-, and low-PAD categories and pooled accordingly. Thirty-five male Wistar rats were randomly assigned to five groups and orally treated with 20% (w/v) PAD-classified honey for four weeks, followed by doxorubicin administration (20 mg/kg, i.p.) to induce hepatorenal toxicity. Serum biochemical markers, oxidative stress indices, and histopathological alterations in liver and kidney tissues were subsequently evaluated. Results: Doxorubicin increased liver and kidney injury markers, oxidative stress parameters, and glucose levels. Medium- and high-PAD honeys improved biochemical homeostasis, enhanced antioxidant defense, and, as confirmed by histopathological analysis, attenuated hepatic and renal degeneration, necrosis, inflammation, and structural damage. Conclusion: High-PAD-score honey, owing to its antioxidant and phenolic properties, may exert protective effects against doxorubicin-induced organ toxicity in experimental models. However, further mechanistic studies and carefully designed investigations are required before any implications for supportive or clinical use can be considered.