Background and Objective:
Malathion, an organophosphate compound, can cause severe damage to vital organs such as the liver. Its toxic effects are mainly mediated through cholinesterase inhibition and the induction of oxidative stress. Hesperidin, a flavonoid with potent antioxidant and anti-inflammatory properties, may play a protective role against such damage. The present study aimed to investigate the protective effects of hesperidin against subacute malathion-induced hepatic injury in female Syrian mice.

Methods:
In this experimental study, thirty-two female Syrian mice were randomly assigned to four groups (n = 8): negative control, malathion control, hesperidin control, and treatment (malathion + hesperidin). Malathion (3 mg/kg) and hesperidin (20 mg/kg) were administered intraperitoneally for 35 consecutive days. Following anesthesia, cardiac blood collection and liver tissue sampling were performed. Data were analyzed using SPSS version 24, with statistical significance set at p < 0.05.

Results:
In the malathion group, serum levels of liver enzymes (ALT, AST, ALP), total and direct bilirubin were significantly increased compared to the control group, accompanied by abnormal histopathological changes. In contrast, these parameters showed a significant reduction in the treatment group (p < 0.05). Total antioxidant capacity (TAC) decreased in the malathion group but increased significantly in the hesperidin and treatment groups. Moreover, malondialdehyde (MDA) levels were elevated in the malathion group but significantly reduced following hesperidin administration.

Conclusion:
Malathion exposure induced marked histopathological alterations and hepatic enzyme disturbances, while hesperidin administration effectively mitigated these adverse effects. Therefore, hesperidin may serve as a promising protective agent against malathion-induced hepatotoxicity.