Topiramate exacerbates liver damage: a study on NAFLD, nitrosative stress and apoptosis

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of obesity. Topiramate (TPM) is an anti-obesity drug. Previously, TPM showed oxidative effect to the liver. On the other hand, its effect on nitrosative stress, inflammation, and apoptosis in healthy and fatty livers remains unclear. Therefore, we aim to fill this gap. Twenty-four male Wistar albino rats were randomly assigned to four groups: Control, Diet, TPM, and Diet + TPM. The diet groups received a high-fat diet for six weeks to induce NAFLD. The TPM groups administered orally (100 mg/kg/d) for an additional 21 days. Rat livers were analyzed for NO, nitrotyrosine, TNF-α, IL-10, caspase 3 and 9, and cytochrome-c (Cyt-c). Liver sections were evaluated immunohistochemically for BAX and BCL-2 expressions. Caspase-3, Caspase-9, and Cyt-c levels were increased, and IL-10 levels were decreased in both the diet and TPM groups. When applied together, Co-administration of a high-fat diet and TPM further elevated Caspase-9 and Cyt-c levels in the Diet + TPM group. Although TNF-α levels were higher in both the diet and TPM groups, statistical significance was attained only in the diet + TPM group. TPM also increased NO and nitrotyrosine levels in both standard and high-fat diet groups. TPM causes liver tissue nitrosative stress, and increased apoptosis regardless of NAFLD. Due to the high occurrence of NAFLD in obese people, it is important to carefully evaluate using TPM as an anti-obesity medicine.