Topiramate’s effects on normal and fatty liver

Abstract

Topiramate (TPM), a carbonic anhydrase (CA) inhibitor, is known for its anti-obesity effect. Even though, nonalcoholic fatty liver disease (NAFLD) is present in 80% of obese patients, TPM’s effects on oxidant-antioxidant parameters and CA activity on fatty liver is not known. 24 Wistar albino rats were divided into four groups: control, TPM, diet, and diet + TPM. Diet groups fed with high-fat diet while control and TPM groups received standard chow for six weeks. Than 100 mg/kg/day TPM (po) was added to TPM groups for 21 days. Rats’ weight and blood glucose levels were monitored weekly, and at the end of the study liver removed for biochemical and histological analysis. TPM eliminated the increases in weight and blood glucose levels caused by high-fat diet. TPM decreased CA activity in all groups. MDA levels increased significantly in TPM and DT groups (p = 0.004; p = 0.008). GSH levels were decreased in the TPM, D and DT groups (p = 0.004; p = 0.015; p = 0.003). Similarly, GPx activity levels were significantly decreased in all groups. Histological evaluation revealed notable infiltration, eosinophilia and cytoplasmic vacuolization in the TPM group. Steatosis and NAFLD activity score (NAS) were higher in the diet group. Ballooning, infiltration and NAS were higher in the diet + TPM group compared to control. CA activity negatively correlated with MDA (p < 0.001), and positively correlated with GSH (p < 0.001). TPM caused oxidant stress and liver damage, which are exacerbated in NAFLD induced rats. Therefore, use of TPM in patients with liver disease should be considered very carefully.

Keywords:

• Topiramate
• nonalcoholic fatty liver disease
• oxidative stress
• carbonic anhydrase
• liver damage

Acknowledgements

We are grateful to Professor Kamer Kılınç for his contribution about biochemical analyses.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data supporting this study are available upon reasonable request.

This study is original and is not under consideration for publication elsewhere or being simultaneously submitted elsewhere. Part of the data contained in this manuscript was presented in 47th National (Turkish) Physiology Congress as poster communication and a short abstract was published in ACTA Physiologica (Jan 2023, Supp 727). We declare no conflict of interests. We received no financial support for this work. The data that support the findings of this study are available from the corresponding author upon reasonable request. This study was approved by the Local Ethics Committee for Animal Experiments of Gazi University, Turkey.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.