Warm alkaline hydrogen peroxide solution as an oxygen-releasing antihypoxic drug: potential benefits and applications

Under conditions of hypoxemia, the brain undergoes hypoxic damage earlier than other tissues of the human body do. Because oxygen naturally reaches the brain with arterial blood, which is enriched with oxygen in the lungs when they are ventilated with breathing gas, cerebral hypoxia has traditionally been attempted by using inhaled oxygen, breathing masks, intubation tubes, and machines designed for artificial lung ventilation and extracorporeal membrane oxygenation. The introduction of oxygen gas into the blood via artificial lung ventilation and extracorporeal membrane oxygenation has accelerated this process in the field of resuscitation but has significantly slowed the search for alternative antihypoxic drugs and methods to combat cerebral hypoxia. Moreover, the problem of controlling cerebral hypoxia has not yet been definitively solved.1 Hypoxic brain damage remains a direct cause of biological death in humans.2 Moreover, hypoxic brain damage can occur when oxygen is administered with artificial lung ventilation in cases of respiratory obstruction, pulmonary edema, bronchiectatic disease, closed pneumothorax, and asphyxia caused by drowning in water or meconium, as well as in cases of blood and/or food mass asphyxia and nonspecific bilateral pneumonia in patients with COVID-19.3-7 Therefore, in recent years, the possibility of replacing gaseous oxygen with a repurposed hydrogen peroxide solution, which allows oxygenation of the blood both through and bypassing the lungs, has been actively studied.4,8-10 Hypoxic brain damage can be pushed back or reduced not only by oxygen gas but also by special hydrogen peroxide solutions administered to the body in several ways. For more than 100 years, solutions of 3–6% hydrogen peroxide have been used as over-the-counter oxidant antiseptics; these solutions are produced with acidic properties and are used at room temperature (24–26°C).4,5 The situation changed after Russian researchers in the early 21st century reported that replacing acidic activity with alkaline activity at pH 8.4 and heating to 37–45°C changed the pharmacological activity of hydrogen peroxide solutions during topical application. Owing to changes in the temperature and physicochemical properties of hydrogen peroxide solutions, several new groups of drugs, including oxygen-releasing antihypoxants for the treatment of coronavirus disease, have been developed. All of them have been combined into one general pharmacological group called “warm alkaline hydrogen peroxide solutions” (WAHPSs).4-6 Safe alkalinization of a hydrogen peroxide solution can be achieved by supplementing it with sodium bicarbonate, since sodium bicarbonate is a natural alkaline buffer in the human body that provides safe alkalinity.4-7 Moreover, alkaline activity results in a nonspecific (physicochemical) saponifying effect on lipid and protein–lipid complexes in the sputum, mucus, serous fluid, purulent mass and blood clots, which promotes their dissolution. Moreover, heating alkaline hydrogen peroxide solution to 37–45°C accelerates saponifying action, promotes dissolution of thick colloidal masses, reduces their viscosity, improves sanitation, and accelerates catalase cleavage of hydrogen peroxide into water and oxygen gas according to the Arrhenius law. Owing to the presence of catalase in many tissues, the formation of oxygen from WAHPS is possible throughout the body. Therefore, the formation of oxygen gas from hydrogen peroxide is possible with the topical application of WAHPSs to any part of the body and under any condition (Figure 1).Figure 1: A warm alkaline solution of hydrogen peroxide in direct interaction with blood, mucus, pus and other tissues instantly turns colloidal fluids into oxygen foam because the hydrogen peroxide in WAHPS is instantly broken down by the action of the tissue enzyme catalase into water and oxygen gas.WAHPS: warm alkaline hydrogen peroxide solutions.The maximum potential oxygen release capacity of WAHPSs is determined by the dose of hydrogen peroxide contained in a selected volume of WAHPSs. Therefore, the greater the oxygen supply to tissues during localized application of WAHPSs is, the greater the volume of drug administered. Consequently, WAHPSs prevent hypoxic damage similar to increasing arterial blood. On this basis, specific WAHPSs can be administered not only by application and inhalation but also via targeted injections into tissue sites that require oxygen delivery to prevent ischemic–hypoxic damage. In addition, drinks can also include hydrogen peroxide for whole-body oxygenation (Additional Table 1).Additional Table 1: Patents for inventions in which hydrogen peroxide acts as an oxygen-releasing antihypoxantWarm alkaline solutions of 0.1–3% hydrogen peroxide can be used for airway healing in respiratory obstruction caused by purulent obstructive bronchitis and/or nonspecific pneumonia in new coronavirus infections. The fact is that subtotal and total airway obstruction by mucus, sputum, pus and/or blood is not eliminated today by traditional mucolytics, expectorant drugs and technologies.3,6 Therefore, urgent airway recanalization and intrapulmonary oxygenation of blood during their use remain unattainable with medications included in the medical standard.3,6 Moreover, aerosol inhalation and intrapulmonary injection of WAHPS provide urgent pyolytic, mucolytic, expectorant, and oxygen-releasing effects within the airways.11 This quickly transforms dense colloidal masses into fluffy oxygen foam within the airways, increasing airway airiness, oxygen absorption into the blood, and blood oxygen saturation through the lungs. Importantly, the intrapulmonary use of WAHPSs reliably decontaminates, disinfects and expectorates the airways, and restores ventilation of the lungs with respiratory gases. Consequently, WAHPS in various formulations represents an uncomplicated oxygen source to prevent or minimize damage to the brain, lungs, and other tissues. For safety reasons, the risk of local irritation, toxicity, and carcinogenic effects of hydrogen peroxide must be addressed in the future when WAHPS is inhaled, consumed, and/or injected. Additional file: Additional Table 1:Patents for inventions in which hydrogen peroxide acts as an oxygen-releasing antihypoxant.