Potential Effect of Fisetin and Curcumin Combination in Alleviating Arsenic Trioxide–Mediated Oxidative Stress and Hepatotoxicity

Arsenic trioxide (As2O3) exposure remains a major public health concern due to its hepatotoxic effects, which are largely mediated by oxidative stress, inflammation, and apoptosis. Natural bioactive compounds such as Fisetin, a flavonoid found in strawberries, apples, onions, and cucumbers, and curcumin, the principal curcuminoid in turmeric (Curcuma longa), are known for their antioxidant and anti-inflammatory properties. However, their combined protective role against arsenic-induced liver injury has not been well established. This study evaluated the combined effects of Fisetin and curcumin on As2O3-induced hepatotoxicity in Wistar rats. Thirty male rats (150–200 g) were divided into six groups (n = 5): control, As2O3 only (20 mg/kg), Fisetin only (100 mg/kg), curcumin only (100 mg/kg), Fisetin + curcumin (100 mg/kg each), and As2O3 (20 mg/kg) + Fisetin (100 mg/kg) + curcumin (100 mg/kg). Treatments were administered orally. Liver weight, oxidative stress markers and inflammatory marker were measured and liver histology. Arsenic trioxide exposure significantly increased Malondialdehyde and C-reactive protein levels, while decreasing liver weight, superoxide dismutase and catalase (p < 0.05). Histological examination revealed extensive hepatic alterations, characterized by hepatocyte abnormalities, sinusoidal dilation, vascular congestion, and steatosis resulting from arsenic trioxide exposure. Treatment with the combination of Fisetin and curcumin after arsenic trioxide exposure significantly improved antioxidant status, reduced inflammation, and restored hepatic architecture. Overall, the findings demonstrate that Fisetin and curcumin in combination exert strong restorative effects against As2O3-induced oxidative stress and hepatotoxicity, suggesting their potential as complementary agents for preventing arsenic-related liver injury.

Key Words: arsenic-trioxide, hepatic injury, oxidative stress, fisetin, curcumin hepatoprotection