Investigation of the Protective Effect of Morin on Oxidative Stress and Apoptosis in Malathion‐Induced Hepatotoxicity in Rats

Malathion (MAL) is a widely used organophosphate pesticide associated with hepatotoxicity through oxidative stress and apoptosis. Morin, a naturally occurring flavonoid, exhibits potent antioxidant and anti-inflammatory properties. This study investigated oxidative stress, inflammatory, and apoptotic alterations induced by acute and subacute MAL exposure in rats and evaluated the potential protective effects of morin. Fifty 3-month-old male Sprague Dawley rats were randomly assigned to six groups: control, morin (200 mg/kg), subacute MAL (150 mg/kg), acute MAL (300 mg/kg), subacute MAL + morin, and acute MAL + morin. At the end of the experimental period, liver tissues and plasma samples were analyzed. Hepatic malondialdehyde (MDA) and glutathione (GSH) levels; catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and glutathione S-transferase (GST) activities; plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities; and tissue acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tumor necrosis factor-α (TNF-α), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), Bax/Bcl-2 ratio and caspase-3 levels were determined. MAL exposure significantly increased MDA, TNF-α, Bax, Bax/Bcl-2 ratio, caspase-3, and liver enzyme activities, while decreasing GSH levels, antioxidant enzyme activities, AChE, BChE, and Bcl-2 levels (p < 0.001). Histopathological findings included hepatocellular swelling, focal necrosis, sinusoidal congestion, periportal infiltration, and bile duct proliferation, with more pronounced lesions in the subacute MAL group. Morin administration markedly attenuated biochemical alterations and improved histopathological damage. These findings demonstrate that MAL induces hepatotoxicity by promoting oxidative stress, inflammation, and apoptosis, whereas morin exerts significant hepatoprotective effects, likely through modulation of antioxidant defense systems and apoptotic pathways.