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How does methylene blue cure cyanide poisoning?

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Methylene Blue, commonly known as Methylthioninium chloride, is a thiazine dye that is used for several purposes, both in medical and non-medical applications. In medicine, two of its approved uses are for treating methemoglobinemia and it has also been used for treating cyanide poisoning.

In this article, we will be exploring how methylene blue is used in treating cyanide poisoning.

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What is Cyanide Poisoning

Cyanide is a poisonous chemical that can be found in a variety of forms. Cyanide can be found in two forms: as a colourless gas cyanogen chloride (CNCl) or hydrogen cyanide (HCN) or as a crystal (potassium cyanide (KCN) or sodium cyanide (NaCN).

The odour of cyanide has been described as “bitter almond,” however it does not always generate an odour, and not everyone can detect it. Cassava, lima beans, and almonds are among the foods and plants that naturally generate them. Apricots, apples, and peaches, for example, have considerable amounts of chemicals that be turned into cyanide in their pits and seeds. At the edible parts of these plants, these chemicals are found in much lower amounts.

The amount of cyanide a person is exposed to, the mode of exposure, and the length of time a person is exposed determine the seriousness of cyanide poisoning. Inhaling cyanide gas causes the most serious harm. Cyanide gas is particularly dangerous in tight spaces because it can become trapped. It hinders the body’s cells from utilising oxygen. It makes the cells cease working and they eventually die. Because the brain and heart require oxygen to function, cyanide is more harmful to them than to other organs.

Cyanides are very poisonous. It inhibits 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 strongly binds to the iron in this protein. When cyanide interacts with this enzyme, it inhibits electron transport from cytochrome c to oxygen. As a result, the electron transport chain is disrupted, and the cell is no longer able to produce ATP aerobically to provide energy. Tissues that rely on aerobic respiration, such as the central nervous system and the heart, are particularly vulnerable. histotoxic hypoxia is indicated by this symptom.

How does methylene blue cure cyanide poisoning?

A lot of research has been done to check the mechanism and efficiency of Methylene Blue against cyanide poisoning. From the research we can conclude that methylene blue helps in stimulating respiration, it restores the oxidation-reduction state and CA2+ Channel Activity

Stimulates Respiration

In the research paper, Methylene Blue as an Antidote for Cyanide Poisoning written by P.J. Hanzlik, it has been mentioned that Methylene Blue’s efficacy in treatment for cyanide poisoning was first demonstrated in 1926 and significantly established in 1930. It stated that Methylene blue stimulated respiration after being suppressed due to exposure to sodium cyanide to the point of enabling 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 normal oxidation-reduction state and CA2+ Channel Activity

In another research paper, Methylene Blue Counteracts Cyanide Cardiotoxicity: Cellular Mechanisms, written by Joseph Y. Cheung et al., it was stated that cyanide poisoning caused by industrial exposure, inhalation of smoke, or bioterrorism causes cardiogenic shock and needs an immediate antidote. ATP levels usually remain normal in the early stages of cyanide exposure. Still, myocyte contractility is decreased, owing to changes in Ca2+ homeostasis caused by changes in the oxidation-reduction environment of ion channels. Methylene blue reduces cyanide toxicity by restoring normal oxidation-reduction state and Ca2+ channel activity.

Adult mouse cardiac myocytes were employed to investigate the biological processes through which Methylene blue enhances myocyte contractility and lowers cardiac arrhythmias after exposure to cyanide. Myocyte contraction and intracellular calcium concentration, transient amplitudes, action potential, depolarization-activated K+ currents, cellular ATP levels, mitochondrial membrane potential, and superoxide levels were all tested to see if they were affected. In an attempt to recreate a therapeutically relevant scenario, three critical experimental circumstances were reproduced that occur in vivo. First, myocytes were administered to NaCN at doses comparable within 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-restricting settings to achieve complete metabolic obstruction.

Many other kinds of research have been done to see if methylene blue (MB) can directly counteract the neurological toxicity of fatal cyanide (CN) overdose.

Restores blood pressure, cardiac contractility and limited O2 deficit

An article titled, Revisiting the physiological effects of methylene blue as a treatment of cyanide intoxication written by Philippe Haouzi and other authors talks about a study that was performed on adult male Sprague-Dawley rats and on HEK293T epithelial cells. All the rats received a lethal infusion of a solution of KCN (0.75 mg/kg/min) and were treated by either saline or MB, at 20 mg/kg. It was found that the animals who were treated with MB 20 mg/kg were all able to survive as the treatment restored their blood pressure, cardiac contractility and limited O2 deficit without any significant methemoglobinemia.

In primary cultures of human foetal neurons intoxicated with Cyanide, Methylene Blue restored NaCN-induced resting membrane potential depolarization and action potential depression. In the Cyanide-intoxicated human SH-SY5Y neuroblastoma cell line, Methylene Blue restored calcium homeostasis. Methylene Blue was found to significantly reduce cyanide neurotoxicity in a dose-dependent manner, avoiding lethal respiratory neuron depression and death.

The above findings prompted 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 against cyanide poisoning cannot be explained by the production of cyanomethemoglobinemia; rather, its potential health effects appear to be related to the distinctive attributes of this redox dye, which, relying on the dosage, can sometimes directly oppose some of the risks of Cyanide’s metabolic depression at the molecular level.

Disclaimer-

The information provided here is based on general knowledge, articles, research publications etc and we do not claim the authenticity of any of the information provided above. We do not claim or suggest/advise any medical, therapeutic, health or nutritional benefits of Methylene blue. We do not supply or promote our Methylene blue product for the applications which are covered by valid patents and which are not approved by the FDA.

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