Butyrate ameliorates lithium-induced cardiometabolic disorders in male Wistar rats

Abstract

BackgroundCardiometabolic disease is becoming a main cause of death worldwide with over ten million fatalities annually. Lithium (Li) has been reported to be one of the major causes of cardiometabolic disorders due to its narrow therapeutic index. Sodium butyrate (NaB) which is a short chain fatty acid is implicated to possess an amazing therapeutic effect against cardiometabolic disorders. As a result, the current study aims to evaluate sodium butyrate impact on lithium-induced cardiometabolic disorders. MethodsTwenty male Wistar rats weighing between 230 and 250 g were used for the experiment. They were grouped into control and treated groups respectively as (CTR; normal chow), Lithium only (Li; 5 mg/kg, po), Sodium butyrate only (NaB) (200 mg/kg, po) and NaB +Lithium (Li; 5 mg/kg +NaB; 200 mg/kg, po) for six weeks, after a week of acclimation; n=5. The animals were anesthetized using sodium pentobarbital at a dose of 50 mg/kg intraperitoneally, blood samples were collected by cardiac puncture and cardiac tissue homogenates were measured for plasma Fasting Blood Sugar (FBS), plasma Insulin, Phosphatidylinositol 3 Kinase (PI3K), Nitric oxide (NO), Glucose-6-phosphate dehydrogenase (G6PDH), Malonyladehyde (MDA), Catalase (CAT), Superoxide Dismutase (SOD), Nicotinamide adenine dinucleotide phosphate (NADPH), Glutathione Peroxidase (GPx), and Adenosine deaminase /Xanthine oxidase /uric acid (ADA/XO/UA) using respective ELISA kits. ResultsThe results showed that lithium significantly increased fasting blood sugar (FBS), plasma insulin, GPx, CAT, SOD, and MDA while causing a statistical reduction in plasma and cardiac concentration of NADPH, G6PDH, PI3K, endothelial nitric oxide synthase (eNOS), and Nitric Oxide (NO) in comparison with the control. However, butyrate attenuated plasma GPx, CAT, SOD, MDA, FBS, plasma insulin and significantly elevated plasma and cardiac PI3K, eNOS, NO, plasma NADPH and G6PDH levels in relation to control. Also no change was observed in the plasma and cardiac ADA/XO/UA following sodium butyrate. ConclusionTherefore, butyrate has a remarkable therapeutic potential in ameliorating lithium induced cardiometabolic disorders through glucometabolic control.