Application of citrate as a tricarboxylic acid (TCA) cycle intermediate, prevents diabetic-induced heart damages in mice

Document Type : Original Article


1 Department of Emergency, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007China

2 Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou, 325305China

3 The Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, 325000China

4 Department of Pain management, Wenzhou Hospital of integrated Chinese and Western Medicine, Wenzhou, 325000 China

5 Wenling First People’s Hospital, The Affiliated Hospital of Wenzhou Medical University, Wenling, 317500


Objective(s):Higher cellular reactive oxygen species (ROS) levels is important in reducing cellular energy charge (EC) by increasing the levels of key metabolic protein, and nitrosative modifications, and have been shown to damage the cardiac tissue of diabetic mice. However, the relation between energy production and heart function is unclear.
Materials and Methods:Streptozotocin (STZ, 150 mg/kg body weight) was injected intraperitoneally once to mice that had been fasted overnight for induction of diabetes. After diabetic induction, mice received citrate (5 µg/kg) through intraperitoneal injection every other day for 5 weeks. The caspase-3, plasminogen activator inhibitor 1 (PAI1), protein kinase B (PKB), commonly known as AKT and phosphorylated-AKT (p-AKT) proteins were examined to elucidate inflammation and apoptosis in the heart. For histological analysis, heart samples were fixed with 10% formalin and stained with hematoxylin-eosin (HE) and Sirius red to assess pathological changes and fibrosis. The expression levels[AGA1]  of marker proteins, tyrosine nitration, activity of ATP synthase and succinyl-CoA:3-ketoacid coenzyme A transferase-1 (SCOT), and EC were measured.
Results:Intraperitoneal injection of citrate significantly reduced caspase-3 and PAI-1 protein levels and increased p-AKT level on the 5th week; EC in the heart was found to be increased as well. Further, the expression level, activity, and tyrosine nitration of ATP synthase and SCOT were not affected after induction of diabetes.
Conclusion: Results indicate that application of citrate, a tricarboxylic acid (TCA) cycle intermediate, might alleviate cardiac dysfunction by reducing cardiac inflammation, apoptosis, and increasing cardiac EC.


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