The Potential of Sorafenib in Preventing Metabolic Syndrome in Rats Fed a High-Fat High-Sucrose Diet

Adnan Iqbal, Rahila Najam, Shabana Simjee, Saira Saeed Khan, Azfar Ather Ishaqui, Salman Ashfaq Ahmed, Zeeshan Ahmed, Shayan Ahmed, Salman Ahmed, Muhammad Osama, Bilal Jawed


The purpose of this study was to investigate the possible preventive role of sorafenib in preventing obesity, hyperlipidemia, and diabetes by exploring its preventive effects. As there is a rapid increase in the number of people being affected by these diseases, there is a need to find new methods to manage them. Sorafenib has been demonstrated to be a potent inhibitor of ABCC10 transmembrane protein in several studies. A recent study has shown that ABCC10 contributes to the pathogenesis of both hyperglycemia and hyperlipidemia. Additionally, many patients who have cancer also are affected by the metabolic syndrome. Thus, cancer patients must take medicines to control high cholesterol and glucose levels, thus increasing the burden of medicines on cancer patients. As sorafenib is an anti-cancer drug and a potent inhibitor of ABCC10, it may prevent metabolic syndrome in cancer patients, thus reducing the burden of additional medications and their adverse effects. This study’s objective was to determine whether sorafenib can lower high lipid and high glucose levels in rats given a high-fat high-sugar diet. There were four groups of the rats: Group I: control (Standard Diet); Group II: diabetic (type-2) rats were given high-fat diet feed and sucrose through drinking water (25% sucrose) for 60 days (HFSD); Group III: diabetic (type-2) rats were given sorafenib 10 mg/kg/d (orally) for 60 days (HFS-S); Group IV: diabetic (type-2) rats were given metformin (50 mg/kg/d). Blood glucose, insulin, triglyceride, cholesterol, and liver enzyme levels were measured. Histopathological analysis of the liver was also conducted using an optical microscope. There was a significant weight reduction when sorafenib was administered to rats. The treatment produces a significant improvement in triglycerides (TG), total cholesterol (TC), and low-density lipoproteins (LDL) (P < 0.05). Furthermore, it also lowers blood glucose levels and improves insulin sensitivity (P < 0.05). Moreover, hepatic steatosis was also prevented by sorafenib in the histopathological analysis of the liver. According to our study, the effects of sorafenib were significant in improving dyslipidemia, hyperglycemia, and insulin sensitivity, as well as preventing the accumulation of fatty deposits in the rats' liver tissue when sorafenib was administered with a high-fat sucrose diet.


Keywords: sorafenib, ABCC10, cancer, hyperlipidemia, metabolic syndrome.

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