Investigation of the protective effect of morin on oxidative stress and apoptosis in malathion-induced hepatotoxicity in rats

Malathion is the most commonly used organophosphate pesticide in agricultural and public health programmes. Morin, on the other hand, is a flavonoid naturally found in plants and attracts attention with its various biological activities, such as antioxidant, anti-inflammatory, anticancer and hepatoprotective properties. The aim of this study was to investigate changes in parameters involved in oxidative stress and apoptosis in acute and subacute malathion-induced hepatotoxicity in rats and to evaluate the potential protective effects of morin against these processes. Fifty 3-month-old male Sprague Dawley rats were used in the study. The groups in the study were: the control group, the morin-treated group (200 mg/kg, gavage, 10 days), the subacute malathion-treated group (150 mg/kg/day, gavage, 21 days), the acute malathion-treated group (300 mg/kg/day, gavage, 2 days), the subacute malathion+morin group, and the acute malathion+morin group. In the subacute malathion+morin group, morin administration was initiated on the 12th day of malathion administration. In the acute malathion+morin group, malathion administration was initiated on the 9th day of morin administration. At the end of the treatments, malondialdehyde (MDA) and glutathione (GSH) levels, glutathione peroxidase (GSH-Px), catalase (KAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities were determined in blood and liver tissue samples. In plasma, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities were analysed. In the liver, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tumour necrosis factor alpha (TNF-α), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 levels were determined using the ELISA method. In the subacute and acute malathion-treated groups, statistically significant increases were observed in MDA, TNF-α, Bax, and caspase-3 levels, as well as AST, ALT, and ALP activities in blood and liver tissue samples, while decreases were observed in GSH, AChE, BChE, Bcl-2 levels, CAT, GSH-Px, SOD, GST, were found to decrease (p < 0.001). Compared to the groups treated with subacute and acute malathion, the groups treated with subacute and acute malathion together with morin showed a significant decrease in MDA, TNF-α, Bax, and caspase-3 levels, as well as plasma AST, ALT, and ALP levels (p < 0.001), while GSH, AChE, and BChE levels, as well as CAT, GSH-Px, SOD, and GST activities (p < 0.001). Our findings indicate that malathion exposure induces oxidative stress and triggers serious biochemical and cellular stress response indicators in the liver and systemic circulation. The activation of apoptosis and inflammatory responses indicate that the liver, as a detoxification organ, is vulnerable to malathion toxicity and suffers cellular damage. Additionally, increased plasma AST, ALT, and ALP activities in the subacute and acute malathion-treated groups are considered another indicator of liver damage. Despite the reported protective effects of morin, there are no studies on its effects against liver damage caused by malathion. However, it has been concluded that morin, which is plant-derived and has multifaceted biological activity, may be a natural protector against pesticide toxicity.