Methylene blue , commonly known as methylthioninium chloride , is a thiazine dye used for a variety of purposes in both medical and non-medical applications. In medicine, two of its approved uses are the treatment of methemoglobinemia , and it has also been used to treat cyanide poisoning.
In this article, we will explore how methylene blue is used in the treatment of cyanide poisoning.
What is cyanide poisoning?
Cyanide is a poisonous chemical that can be found in various forms. Cyanide can be found in two forms: as a colorless gas (cyanogen chloride (CNCl) or hydrogen cyanide (HCN)) or as a crystal (potassium cyanide (KCN) or sodium cyanide (NaCN).
The smell of cyanide has been described as “bitter almond,” but it does not always produce an odor and not everyone can detect it. Cassava, beans, and almonds are among the foods and plants that produce it naturally. Apricots, apples, and peaches, for example, have considerable amounts of chemicals that can be converted to cyanide in their pits and seeds. In the edible parts of these plants, these chemicals are found in much smaller amounts.
The amount of cyanide a person is exposed to, the mode of exposure, and the length of time they are exposed determine the severity of cyanide poisoning. Inhaling cyanide gas causes the most serious damage. Cyanide gas is especially dangerous in confined spaces because it can become trapped. It prevents the body's cells from using oxygen. It causes cells to stop working and eventually die. Because the brain and heart need oxygen to function, cyanide is more damaging to them than to other organs.
Cyanides are very poisonous. They inhibit cytochrome c oxidase (enzyme), which is located in the membrane of mitochondria in eukaryotes and serves as the fourth complex in the electron transport chain (ETC). It binds tightly to iron in this protein. When cyanide interacts with this enzyme, it inhibits the transport of electrons from cytochrome c to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer produce ATP aerobically to provide energy. Tissues that rely on aerobic respiration, such as the central nervous system and heart, are particularly vulnerable. Histotoxic hypoxia is indicated by this symptom.
How does methylene blue cure cyanide poisoning?
Many researches have been conducted to check the mechanism and efficacy of methylene blue USP against cyanide poisoning. From the research, we can conclude that methylene blue helps to stimulate respiration, restores oxidation-reduction state and Ca2+ channel activity.
Stimulates breathing
In the research article, Methylene Blue as an Antidote for Cyanide Poisoning written by P.J. Hanzlik, it has been mentioned that the efficacy of methylene blue in treating cyanide poisoning was first demonstrated in 1926 and was significantly established in 1930. Methylene blue was claimed to stimulate respiration after it had been suppressed due to exposure to sodium cyanide to the extent of allowing an animal to survive an otherwise fatal dose of cyanide. The effect of such a dose of cyanide was significantly reduced. The animal survived if methylene blue, 10 MGM, per kilo, was injected into the femoral vein 10 minutes before or not more than 2 minutes after the cyanide.
Restores the normal oxidation-reduction state and Ca2+ channel activity
In another research article, Methylene Blue Counteracts Cyanide Cardiotoxicity: Cellular Mechanisms , written by Joseph Y. Cheung, it was stated that cyanide poisoning caused by industrial exposure, smoke inhalation, or bioterrorism causes cardiogenic shock and needs an immediate antidote. ATP levels typically remain normal in the early stages of cyanide exposure. Even so, myocyte contractility is decreased due to changes in Ca2+ homeostasis caused by changes in the redox environment of ion channels. Methylene blue reduces cyanide toxicity by restoring the normal redox state and Ca2+ channel activity.
Adult mouse cardiac myocytes were employed to investigate the biological processes through which methylene blue enhances myocyte contractility and reduces cardiac arrhythmias following cyanide exposure. Myocyte contraction and intracellular calcium concentration, transient amplitudes, action potential, depolarization-activated K+ currents, cellular ATP levels, mitochondrial membrane potential, and superoxide levels were tested to see if they were affected. In an attempt to recreate a therapeutically relevant scenario, three critical experimental circumstances that occur in vivo were reproduced. First, myocytes were administered NaCN at doses comparable to in vivo poisoning that could be reversed with standard antidotes, limiting myocyte exposure to the high micromolar range of NaCN. Second, previous studies on CN toxicity employed glycolysis restriction settings to achieve complete metabolic blockage.
Many other types of research have been done to see if methylene blue (MB) can directly counteract the neurological toxicity of a lethal cyanide (CN) overdose.
Restores blood pressure, cardiac contractility and limits O2 deficit
An article titled, Revisiting the Physiological Effects of Methylene Blue as a Treatment for Cyanide Poisoning written by Philippe Haouzi et al. discusses a study that was performed on adult male Sprague-Dawley rats and HEK293T epithelial cells. All rats received a lethal infusion of a KCN solution (0.75 mg/kg/min) and were treated with either saline or MB, at 20 mg/kg. It was found that animals that were treated with MB 20 mg/kg were able to survive as the treatment restored their blood pressure, cardiac contractility, and limited O2 deficit without any significant methemoglobinemia.
In primary cultures of cyanide-intoxicated human fetal neurons, methylene blue restored NaCN-induced resting membrane potential depolarization and action potential depression. In the cyanide-intoxicated human neuroblastoma cell line SH-SY5Y, methylene blue restored calcium homeostasis. Methylene blue was found to significantly reduce cyanide neurotoxicity in a dose-dependent manner, preventing lethal depression of respiratory neurons and death.
The above findings led us to consider the possible role of methylene blue in the treatment of cyanide poisoning. The mechanisms of methylene blue's properties as an antidote to cyanide poisoning cannot be explained by the production of cyanmethemoglobinemia; rather, its potential health effects appear to be related to the distinctive attributes of this redox dye, which, depending on the dose, can sometimes directly counteract some of the risks of cyanide metabolic depression at the molecular level.
