Abstract

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.