Ischemia–reperfusion injury (IRI) is a common phenomenon that develops both from natural causes and during major operations. Many intracellular processes mediated by calcium ions are involved in the development of IRI. Currently, chemical calcium channel blockers are used but they have a number of limitations. In this article, we study the effect of the omega-hexatoxin-Hv1a peptide toxin, an alternative to chemical calcium channel blockers, on the mechanisms of IRI development in epithelial cell culture. The toxin was produced using solid phase peptide synthesis. IRI was caused by deprivation of glucose, serum and oxygen. The data obtained demonstrate that the omega-hexatoxin-Hv1a toxin in nanomolar concentrations is able to prevent the development of apoptosis and necrosis in epithelial cells by reducing the concentration of calcium, sodium and potassium ions, as well as by delaying rapid normalization of the pH level, affecting the mitochondrial potential and oxidative stress. This toxin can be used as an alternative to chemical calcium channel blockers for preventing tissue and organ IRI due to its low-dose requirement and high bioavailability.

Ischemia-reperfusion injury (IRI) is an irreversible functional and structural injury. Restoration of normal oxygen concentration exacerbates the emergence and development of deadly cells. One of the possible moments of reperfusion damage to cells is an increase in the intracellular concentration of sodium ions. In this article, we study the mu-agatoxin-Aa1a, a modulator of sodium channels, on the processes of IRI cells damage. The toxin was synthesized using an automatic peptide synthesizer. Hypoxia was induced by reducing the content of serum and oxygen in the CHO-K1 culture. The influence of the toxin on the level of apoptosis; intracellular concentration of sodium, calcium, and potassium ions; intracellular pH; totality of reactive oxygen species (ROS), nitric oxide (NO), and ATP; and changes in the mitochondrial potential were studied. The experiments performed show that mu-agatoxin-Aa1a effectively prevents IRI of cells. Toxin reduces the level of apoptosis and prevents a decrease in the intracellular concentration of sodium and calcium ions during IRI. Mu-agatoxin-Aa1a contributes to the maintenance of elevated intracellular pH, reduces the intracellular concentration of ROS, and prevents the decrease in intracellular NO concentration and mitochondrial potential under conditions of reoxygenation/reperfusion. An analysis of experimental data shows that the mu-agatoxin-Aa1a peptide has adaptogenic properties. In the future, this peptide can be used to prevent ischemia/reperfusion tissue damage different genesis.

Myocardial infarction is one of the common cardiovascular diseases. Sodium overload in the myocardium is another of the most important mechanisms underlying ischemia/reperfusion injury. Na⁺ entry into the cell through ion channels can be controlled using peptide toxins targeting ion channels. In our work, we analyze the use of mu-agatoxin-Aa1a, as a sodium channel modulator, as a cytoprotective agent in ischemia/reperfusion injury. For IRI modeling in vitro, the H9C2 culture was placed under oxygen-glucose deprivation conditions followed by reperfusion. Cell death and ion dynamics were recorded using a fluorescent plate reader. Reversible myocardial ischemia of rats in vivo was created by applying an occluder under the main branch of the left coronary artery. Histological and biochemical changes were recorded. The study demonstrated the ability of mu-agatoxin-Aa1a myocardial cells to adapt to rapidly changing extracellular conditions upon restoration of normal blood flow after a period of ischemia. Thus, the study allows us to consider mu-agatoxin-Aa1a as a biologically active molecule with a targeted effect to enhance the adaptation of cardiomyocytes to OGD/reperfusion conditions.