Introduction
Methylthioninium chloride, also known as methylene blue, is a thiazine dye with various uses in medical and non-medical applications. For example, it has been used to treat cyanide poisoning and methemoglobinemia (a blood condition where excessive amounts of methemoglobin are generated), two of its approved medical services.
What Is Cyanide Poisoning?
A dangerous chemical called cyanide comes in several forms. Cyanide can be found in two other forms: as a crystal of potassium cyanide (KCN) or sodium cyanide (NaCN) or as an invisible gas such as cyanogen chloride (CNCl) or hydrogen cyanide (HCN).
Although cyanide has been characterized as having a "bitter almond" odor, this is not always the case; not everyone can smell it. In addition, they are produced naturally by various foods and plants, including cassava, lima beans, and almonds. For instance, the pits and seeds of apricots, apples, and peaches contain certain compounds that can be converted to cyanide. However, these compounds are present in much lower concentrations in the edible sections of these plants.
The severity of cyanide poisoning depends on the amount of cyanide a person is exposed to, the mode of exposure, and the duration. The worst damage is caused by inhaling cyanide gas. Cyanide gas can become trapped, which makes it highly deadly in confined places. It prevents cells in the body from using oxygen. The cells gradually stop functioning as a result, and they die. Cyanide is more toxic to the brain and heart than other organs since they need oxygen to function properly.
Cyanides are highly poisonous. It affects the fourth complex of the electron transport chain, cytochrome c oxidase, an enzyme found in the mitochondrial membrane of eukaryotes (ETC). Cyanide interferes with this enzyme, preventing the transfer of electrons from cytochrome c to oxygen. The electron transport chain is then broken, which prevents the cell from aerobically producing ATP (adenosine triphosphate) to supply energy. Particularly vulnerable are the heart and central nervous system tissues that depend on aerobic respiration. This symptom is indicative of hypoxia (reduced oxygen concentration at the tissue level).
What Are the Medical Uses of Methylene Blue?
The following are the medical uses of Methylene blue:
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Methemoglobinemia: When there is too much methemoglobin in the blood, methemoglobinemia develops. Exposure to specific drugs or harmful compounds, such as nitrates, can cause methemoglobinemia. Although methemoglobin is a kind of hemoglobin, it does not aid in oxygen transport hemoglobin does. Small amounts of methemoglobin are found in the blood. But as methemoglobin levels increase, it is more difficult to carry oxygen. It causes symptoms including blue or pale skin and an oxygen deficiency throughout the body. Methylene blue injection is used to treat methemoglobinemia. Methylene blue is presently mainly used to treat methemoglobinemia. Methylene blue first transforms into leucomethylene blue when administered intravenously as an antidote, and leucomethylene blue then changes the heme group from methemoglobin to hemoglobin. The half-life of methemoglobin can be reduced by methylene blue from hours to minutes. Methemoglobin is transformed by methylene blue into a more efficient form of hemoglobin that distributes oxygen more effectively throughout the body.
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Cyanide Poisoning: Cyanide has been used as a stand-in for anoxia in several experimental settings for more than a century because physiologists believed that blocking the metalloenzymes found in mitochondrial complexes by cyanide would replicate the acute effects of a reduction in oxygen supply. The cardiogenic shock from cyanide poisoning, which can occur for various reasons, including industrial exposure, smoke inhalation, or bioterrorism, calls for an emergency antidote. By re-establishing oxidation-reduction equilibrium and calcium channel activity, methylene blue lessens the toxicity of cyanide. However, it is no longer advised to be used.
How Does Methylene Blue Cure Cyanide Poisoning?
Many studies have examined the workings and effectiveness of methylene blue as a cyanide poisoning preventative. According to the research, methylene blue aids in promoting respiration, restores the oxidation-reduction state, and increases calcium channel activity.
Stimulates Respiration:
The effectiveness of methylene blue as a cure for cyanide poisoning was first proved in 1926 and was firmly confirmed in 1930, according to one of the research publications. It was claimed that methylene blue stimulated breathing after it had been repressed by exposure to sodium cyanide to the extent that it allowed an animal to survive a dose of cyanide that would have otherwise killed it. The impact of a high cyanide dose was greatly diminished. The animal survived when methylene blue, 10 mgm per kilogram, was injected into the femoral vein 10 minutes before or no later than 2 minutes after the cyanide.
Restores Normal Oxidation-Reduction State and CA2+ Channel Activity:
Another study claimed that cardiogenic shock from cyanide poisoning brought on by occupational exposure, smoke inhalation, or bioterrorism requires an emergency antidote. However, early on with cyanide exposure, ATP levels often remain normal. Nevertheless, alterations in calcium homeostasis caused by modifications to the oxidation-reduction environment of ion channels result in a reduction in myocyte contractility. By re-establishing a healthy oxidation-reduction state and calcium channel functioning, methylene blue lessens the toxicity of cyanide.
The molecular mechanisms through which methylene blue improves myocyte contractility and reduces cardiac arrhythmias following exposure to cyanide were examined using adult mouse cardiac myocytes. Transient amplitudes, action potential, depolarization-activated K+ currents, cellular ATP levels, mitochondrial membrane potential, and superoxide levels were all examined to determine whether they were impacted. In addition, three crucial experimental conditions in vivo were replicated to mimic a therapeutically relevant setting. First, myocyte exposure to NaCN was restricted to the high micromolar range by giving myocytes amounts comparable to in vivo poisoning that can be treated with common antidotes. Second, earlier investigations on cyanide toxicity used glycolysis-restricting conditions to accomplish total metabolic blockage.
Restores Blood Pressure, Cardiac Contractility, and Limited Oxygen Deficit:
HEK293T epithelial cells and adult male Sprague-Dawley rats were used in one experiment. All rats were given either saline or methylene blue at a dose of 20 mg/kg after receiving a fatal infusion of a KCN solution (0.75 mg/kg/min). It was discovered that all of the animals given methylene blue in the dosage of 20 mg/kg therapy could live since the medication restored their blood pressure, cardiac contractility, and minimal oxygen deficit without significantly increasing methemoglobinemia.
Methylene blue reversed NaCN-induced resting membrane potential depolarization and action potential depression in primary cultures of cyanide-intoxicated human fetal neurons. In addition, methylene blue restored calcium homeostasis in the human SH-SY5Y neuroblastoma cell line exposed to cyanide. Finally, it was discovered that, in a dose-dependent way, methylene blue significantly reduced cyanide neurotoxicity, preventing fatal respiratory neuron depression and death.
According to the findings, methylene blue can treat cyanide poisoning. However, there is not enough evidence to fully explain the mechanisms underlying methylene blue's ability to treat cyanide poisoning; instead, its potential health effects seem to be linked to the unique properties of this redox dye, which, depending on dosage, can occasionally directly counteract some of the risks of cyanide's metabolic depression at the molecular level.
Conclusion
Methylene blue is a thiazide salt that is employed as both medicine and dye. Methylene blue changes the ferric iron in hemoglobin to ferrous iron. Therefore, it is used as a medicine to treat methemoglobinemia. Methylene blue has been widely used to treat cyanide poisoning, which can occur for various reasons.
