Why Potentized ‘Snake Venom’ Is Not Effective In Managing Acute Emergencies Of Snake Bites?

Can you confidently treat a case of venomous snake bite with the potentised snake venom”?

According to my concept of MIT, potentization involves molecular imprinting, and ‘molecular imprints’ are the active principles of potentized drugs. Since ‘molecular imprints are ‘artificial binding sites’ or ‘artificial keyholes’ exactly fitting to the original molecules used for imprinting, molecular imprints should be capable of ‘binding’ and ‘deactivating’ them. That means, if MIT concept is correct, potentized drugs should antidote ‘original drug molecules’ used for imprinting.

In this context, the question raised above is very much relevant. Can anybody dare to treat a case of snake bite using potentized snake venom?

To answer this question, we have to go deeper into the molecular mechanisms involved in poisonous effects of snake venom, as well as potentization. It will lead us to answering many unanswered questions involved in homeopathic potentization and therapeutics.

When a snake bites us, it injects its venom into our blood stream. Snake venom is highly modified saliva containing zootoxins. The glands which secrete the zootoxins are a modification of the parotid salivary gland of other vertebrates. Venoms contain more than 20 different compounds, mostly proteins and polypeptides. It is a complex mixture of proteins, enzymes, and various other substances. The proteins are responsible for the toxic and lethal effect of the venom and its function is to immobilize prey, enzymes play an important role in the digestion of prey, and various other substances are responsible for important but non-lethal biological effects. Some of the proteins in snake venom are very particular in their effects on various biological functions including blood coagulation, blood pressure regulation, transmission of the nervous or muscular impulse and have turned out to be pharmacological or diagnostic tools or even useful drugs.

Proteins constitute 90-95% of venom’s dry weight and they are responsible for almost all of its biological effects. Among hundreds, even thousands of proteins found in venom, there are toxins, neurotoxins in particular, as well as nontoxic proteins, and many enzymes, especially hydrolithic ones. Enzymes make-up 80-90% of viperid and 25-70% of elapid venoms: digestive hydrolases, L-amino acid oxidase, phospholipases, thrombin-like pro-coagulant, and kallikrein-like serine proteases and metalloproteinases (hemorrhagins), which damage vascular endothelium. Polypeptide toxins include cytotoxins, cardiotoxins, and postsynaptic neurotoxins, which bind to acetylcholine receptors at neuromuscular junctions.

Compounds with low molecular weight include metals, peptides, lipids, nucleosides, carbohydrates, amines, and oligopeptides, which inhibit angiotensin converting enzyme and potentiate bradykinin. Phosphodiesterases interfere with the prey’s cardiac system, mainly to lower the blood pressure. Phospholipase A2 causes hemolysis by lysing the phospholipid cell membranes of red blood cells. Amino acid oxidases and proteases are used for digestion. Amino acid oxidase also triggers some other enzymes and is responsible for the yellow colour of the venom of some species. Hyaluronidase increases tissue permeability to accelerate absorption of other enzymes into tissues. Some snake venoms carry fasciculins, like the mambas, which inhibit cholinesterase to make the prey lose muscle control.

Snake toxins vary greatly in their functions. Two major classifications of toxins found in snake venoms include neurotoxins (mostly found in elapids) and hemotoxins (mostly found in viperids). However, there are exceptions – an African spitting cobra Naja nigricollis’s venom consists mainly of hemotoxins, while the Mojave rattlesnake’s venom is primarily neurotoxic. However, there are numerous other different types of toxins which both elapids or viperids may carry.

Snake venom contains various neurotoxic, cardiotoxic, cytotoxic and haematotoxic substances.

Fasciculins: These toxins attack cholinergic neurons by destroying acetylcholinesterase. ACh therefore cannot be broken down and stays in the receptor. This causes tetany, which can lead to death. The toxins have been called fasciculins since after injection into mice, they cause severe, generalized and long-lasting fasciculations.

Dendrotoxins: Dendrotoxins inhibit neurotransmissions by blocking the exchange of + and – ions across the neuronal membrane lead to no nerve impulse. So they paralyse the nerves.

α-neurotoxins: This is a large group of toxins, with over 100 postsynaptic neurotoxins having been identified and sequenced. α-neurotoxins also attack cholinergic neurons. They mimic the shape of the acetylcholine molecule and therefore fit into the receptors. They block the ACh flow causing feeling of numbness and paralysis.

Phospholipases: Phospholipase is an enzyme that transforms the phospholipid molecule into a lysophospholipid. The new molecule attracts and binds fat and ruptures cell membranes.

Cardiotoxins: Cardiotoxins are components that are specifically toxic to the heart. They bind to particular sites on the surface of muscle cells and cause depolarisation The toxin prevents muscle contraction. These toxins may cause the heart to beat irregularly or stop beating, causing death.

Haemotoxins: The toxin causes haemolysis, or destruction of red blood cells.

Lethal effects of venoms are due to these toxic substances which are complex protein molecules. During snake bite, these proteins are injected into the body of the prey.

Snake venom is not dangerous if ingested through alimentary tract, instead of directly injecting into blood stream. It will be digested by digestive enzymes in our intestinal tract and absorbed as aminoacids. Snake venom is a nutritious food like eggs, if cooked and ingested. We know, egg white may be very toxic if injected directly into blood stream.

When snake venom is subjected to potentization, initially the protein molecules in the venom undergo a process called ‘denaturation’.

Now we have to learn something about protein structures and phenomenon of ‘denaturation’.

Proteins are amino acid polymers. A protein is created by ribosomes that “read” RNA that is encoded by codons in the gene and assemble the requisite amino acid combination from the genetic instruction, in a process known as translation. The newly created protein strand then undergoes posttranslational modification, in which additional atoms or molecules are added, for example copper, zinc, or iron. Once this post-translational modification process has been completed, the protein begins to fold (sometimes spontaneously and sometimes with enzymatic assistance), curling up on itself so that hydrophobic elements of the protein are buried deep inside the structure and hydrophilic elements end up on the outside. The final shape of a protein determines how it interacts with its environment. The biological properties of proteins are due to their complex tertiary structure and three dimensional folding.

When a protein is denatured, the secondary and tertiary structures are altered but the peptide bonds of the primary structure between the amino acids are left intact. Since all structural levels of the protein determines its function, the protein can no longer perform its function once it has been denatured. This is in contrast to intrinsically unstructured proteins, which are unfolded in their native state, but still functionally active.

Denatured proteins can exhibit a wide range of characteristics, from loss of solubility to communal aggregation. Communal aggregation is the phenomenon of aggregation of the hydrophobic proteins to come closer and form the bonding between them, so as to reduce the total area exposed to water.

Ethyl alcohol, used as part of medium for potentization, is a very powerful ‘denaturing agent’ for protein molecules. Hence, toxic protein molecules contained in the snake venom undergo a process of ‘denaturation’ when added to alcohol-water mixture for potentization. It is these ‘denatured’ protein molecules that undergo ‘molecular imprinting’ during potentization.

It is now obvious why we cannot treat snake bites using potentized snake venom. Snake venom directly injected into the body during snake bite acts lethally due to the enzymes which are protein molecules. If we could prepare ‘molecular imprints’ of these toxic enzyme molecules without ‘denaturation’, those molecular imprints could have been used to treat snake bites effectively.

Same time, we can manage non-lethal biological effects of snake bites, which are caused by non-protein constituents of snake venom, using potentized venoms.

Obviously, symptoms produced by crude venom administered by oral route, alcoholic preparation of venom administered by oral route, and directly injected into the body during snakebite will be different from one another. That is why our provings never produce all the toxicological symptoms of snake bite.

This is applicable to all drug substances of protein nature, which would undergo denaturation at the initial stages of potentization, when added to water-ethyl alcohol medium. We have to remember this fact when discussing potentized drugs containing enzymes and other complex protein molecules.

This understanding also prompts us to search for other potential imprinting media that do not make molecular changes in proteins.