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Background: Metformin (MET) is a dietary polyphenolic compound that exhibits anti-inflammatory and antioxidant properties. This study evaluated the protective effects of MET in both in vitro and in vivo models against potassium bromate (KBrO3)-induced hepatotoxicity. Hepatic cells were exposed to KBrO3 with or without metformin (20, 40, and 60 µM), and cell viability and Reactive Oxygen Species levels were assessed. In vivo, rats were divided into five groups: control, KBrO3, and KBrO3 with metformin (25, 50, and 100 mg/kg). Liver and blood samples were analyzed for histological changes, oxidative stress markers, lipid peroxidation, liver enzymes, and PI3K/Akt signaling.
Results: KBrO3 exposure significantly decreased cell viability and increased ROS levels. Co-treatment with MET dose-dependently restored cell viability, with 60 µM MET achieving approximately 80% viability. Metformin also reduced ROS levels, with mean fluorescence intensity approaching control values at higher concentrations. In the in vivo study, KBrO3 exposure elevated lipid peroxidation markers, depleted antioxidant enzyme activities, and triggered oxidative stress and inflammation. Metformin significantly alleviated histological liver damage, suppressed proinflammatory cytokines, enhanced antioxidant enzyme activities, and modulated the PI3K/Akt signaling pathway to promote cell survival and reduce oxidative injury.
Conclusions: Metformin effectively protects hepatic cells against KBrO3-induced cytotoxicity by improving cell viability and reducing Reactive Oxygen Species levels. Metformin successfully mitigates KBrO3-induced hepatic injury by reducing oxidative stress, modulating inflammatory pathways (NF-kB), and regulating the PI3K/Akt signaling cascade, offering molecular evidence of its hepatoprotective effects.
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