Professor Wuhan University of Technology, United States
Introduction: Iron homeostasis is critical for physiological functions. Oxidative stress brought on by iron overload harm tissues and organs, such as the liver, heart, and bones. Patients with hemoglobinopathies, hereditary hemochromatosis, older males, and postmenopausal women are frequently affected by iron overload. Deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX) are clinical iron chelator. DFO has a quick metabolism, a short half-life, and limited absorption. Excessive dosages of treatment put a significant strain on the body and increase the possibility of adverse effects such as skeletal abnormalities, allergic responses, and growth retardation. Although oral DFP and DFX have shown significant therapeutic effects, some reports have reported adverse effects such as gastrointestinal bleeding, thrombocytopenia and granulocytopenia, as well as renal toxicity. Therefore, there is an urgent need to search for drugs with low toxicity, good chelating ability, and antioxidant capacity to treat iron overload.
Materials and
Methods: The synthesis of hyperbranched poly citric acid (PCA) involves melting polycondensation using monomers of glycerol and citric acid at a molar ratio of 8:1. Glycerol and citric acid monohydrate were combined in a single-necked bottle and heated to 90 °C in an oil bath with magnetic stirring. A viscous light-yellow material (hyperbranched poly citric acid, PCA) was formed after freeze-drying. Therapeutic mechanism of iron overload was investigated by iron chelation, ROS scavenging, in vitro cell and in vivo liver, bone model.
Results, Conclusions, and Discussions: Results and
Discussion: Evaluation of in vitro results showed that PCA has good iron chelation and ROS scavenging abilities. The cell results indicated that PCA inhibited iron overload-induced apoptosis, ROS production, and mitochondrial dysfunction, and enhanced osteogenic mineralization ability. Furthermore, PCA increased ATP synthesis, which is helpful for improving GSH content and reducing oxidative stress damage caused by iron overload. The bone loss model and liver injury model of mice revealed the potential of PCA in iron overload treatment. PCA mitigated bone loss and restored liver injury. Moreover, we also found that PCA remarkably reduced iron accumulation in bone and liver.
Conclusions: In conclusion, we demonstrated the therapeutic effects of PCA on iron overload both in vivo and vitro. PCA has a dual function, treating oxidative stress damage of iron overload-induced via energy metabolism and iron chelation. Furthermore, PCA showed the potential in osteogenic mineralization, offering novel treatments for bone diseases associated with iron overload. These findings suggest that PCA may be a novel approach to for treating iron overload.
Acknowledgements (Optional): This work was supported by grants from the National Natural Science Foundation of China (32201109, 51772233).
