The effects of dasatinib and quercetin on biochemical pathways in rats with metaboli̇c syndrome

Metabolic syndrome (MetS), a frequently encountered endocrine disorder today, is a combination of systemic disorders such as impaired insulin resistance, abdominal obesity, dyslipidemia, hypertension, coronary artery disease and increased systematic inflammation. Current therapeutic modalities have not provided the expected level of benefit due to the unclear mechanism of MetS. In recent years, dasatinib, a tyrosine kinase inhibitor used in chronic myeloid leukemia patients, has been shown in case reports to improve insulin resistance and contribute to glycemic control with its senolytic effect. In addition, studies with quercetin, a polyphenol, have shown that MetS and its complications are reduced, insulin sensitivity is increased and glucose levels are improved. In our study, we aimed to investigate the effects of dasatinib and quercetin separately and in combination on the pathways that make up the components of MetS and to evaluate their contribution to treatment. In our study, 40 8-week-old Sprague-Dawley female rats were used and they were divided into control, MetS, MetS + Dasatinib, MetS + Quercetin, Mets + Dasatinib + Quercetin (combined) groups. To induce MetS in rats, 20% fructose was added to drinking water and given ad libitum. Dasatinib (5 mg/kg) and quercetin (50 mg/kg) were administered by oral gavage every 2 weeks for 3 consecutive days for 8 weeks. At the end of the 8-week experimental period, blood, liver and kidney tissue samples were taken from the rats. In the samples taken, Triglyceride, Total cholesterol, HDL-C, LDL-C, VLDL-C and Uric acid autoanalyzer and Insulin, Adiponectin, TNF-α, IL-1β, IL-10, FABP4, eNOS, NF-κB and PDGFR- β was analyzed by ELISA method. Compared to controls, in the MetS group; While significant changes were observed in the levels of FABP4, IL-1β, NF-κB, PDGFR-β in plasma tissue, significant differences were detected in the groups receiving quercetin and combined treatment for the same parameters compared to the MetS group. While significant changes were observed in insulin, adiponectin and TNF-α levels in the MetS group compared to the control group in liver tissue, no significant differences were observed in these parameters in the treatment groups except TNF-α. Additionally, serum HDL-C, VLDL-C and Triglyceride levels were found to change significantly in the MetS group compared to the control group. While HDL-C levels were improved in the treated groups, the expected results were not obtained in the others. In conclusion; It has been shown by biochemical evaluation results that quercetin and combined treatments have a curative effect on MetS, and this effect cannot be achieved in dasatinib treatment. Key Words: Metabolic Syndrome, Insulin Resistance, Dasatinib, Quercetin