Hesperidin Protects Mitochondrial Permeability Transition Pore of Rat Liver from Toxicity of High-Glucose Concentration and Some Heavy Metals

The mitochondrial membrane permeability transition pore is a transmembrane protein found in the inner membrane of the mitochondria. This protein pore is normally closed, but it opens when the intracellular calcium concentration rises. Apoptosis is associated with pore opening. Heavy metals (including lead, aluminum, and mercury) and high glucose concentrations have been linked to the opening of the mitochondrial membrane permeability pore via the oxidative stress pathway. Hesperidin is a bioflavonoid and a powerful antioxidant found naturally in fruit that can help reduce oxidative stress. This study was designed to look into the protective role of hesperidin on high-glucose concentrations and some heavy metals on the permeability transition pore of the rat mitochondria. Hesperidin was tested for its ability to protect the MMPT pore, mitochondrial lipid peroxidation, cytochrome c release, caspase 3 and 9, and calcium ATPase using standard protocols. Hesperidin was also docked with calcium ATPase, caspase 3, and caspase 9. Hesperidin inhibited pore opening in a concentration dependent manner, according to the findings. Hesperidin also protected mitochondrial integrity, as measured by lipid peroxidation, cytochrome c release, and the activities of caspase 3 and 9, as well as calcium ATPase. Docking studies revealed that hesperidin has a high affinity for calcium ATPase, caspase 3, and caspase 9. As a result, it could be argued that hesperidin is beneficial in treating mitochondrial diseases as well as liver diseases.