Gadolinium Poisoning, Gadolinium Toxicity

Gadolinium Poisoning, Gadolinium Toxicity
Most of the known toxicity of the free Gd3+ ion is related to 2 properties: its insolubility at physiologic pH, resulting in very slow systemic excretion; and an ionic radius close to that of Ca2+ (Gd3+ = 107.8 pm and Ca2+ = 114 pm) that allows Gd3+ to compete biologically with Ca2+.3,
Gadolinium is a well-known blocker of many types of voltage-gated calcium channels at very low concentrations, and consequently, it can inhibit physiologic processes such as contraction of smooth, skeletal, and cardiac muscles; transmission of nerve impulses; and blood coagulation. It also inhibits the activity of certain enzymes such as Ca2+-activated-Mg2+-adenosine triphosphatase, some dehydrogenases and kinases, and glutathione S-transferases. It also acts as an agonist on the calcium-sensing receptors.Gadolinium may also increase the expression of some cytokines, inhibit mitochondrial function, and induce oxidative stress.
Major lesions related to single-dose administration of gadolinium chloride (0.07–0.35 mmol/kg) in rats consist of mineral deposition in capillary beds, phagocytosis of minerals by macrophage-like cells, hepatocellular and splenic necrosis followed by dystrophic mineralization, decreased platelet numbers, and increased coagulation times.46 Gadolinium is also a potent inhibitor of the reticuloendothelial system. All GBCAs and gadolinium chloride have been found to stimulate fibroblast proliferation in tissues taken from healthy subjects.This last process may be a major factor responsible for NSF because proliferation of CD34+ fibroblasts is the hallmark histologic feature of this disease.

Gadolinium Toxicity and Nephrogenic Systemic Fibrosis
Free gadolinium (Gd3+) is a very toxic heavy metal because its ionic radius is very similar to that of calcium. Free gadolinium can block calcium channels and inhibit nerve transmissions, muscle contraction, blood coagulation, and mitochondrial function. Gadolinium can also replace calcium in bone. Studies on rats showed that only 1-3% of injected free gadolinium is excreted daily with a majority deposited in bone, kidney, and liver. Even though GBCAs are considered safe, there is still the possibility that some of the dose will de-chelate to free gadolinium, especially with linear GBCAs. A condition called Nephrogenic Systemic Fibrosis (NSF) was linked to the use of GBCAs in patients with renal insufficiency. NSF results in free gadolinium accumulation in the kidney, heart, bones, lungs, and skin, usually resulting in death. The half-life of GBCAs is significantly increased in renally impaired patients, resulting in a greater release of free gadolinium due to the contrast agent remaining in the body for a longer period. The onset of symptoms from NSF is usually weeks to months, but in some cases has occurred years after administration [17]. Once this connection was made, screening for renal insufficiency became an important part of GBCA administration. There has been a major shift moving away from linear GBCAs due to de-chelation concerns.
Gadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed “gadolinium storage condition”. The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed “gadolinium deposition disease”. Most advanced way is to use HOPO Chelator, also 3,4,3-Li(1,2-HOPO) cas 110874-36-7 as Gadolinium chelating agent.

How Gadolinium Poisoning Occurs During an MRI?
Magnetic resonance imaging machines (MRI) are tube-shaped magnets that are large enough for a person to fit inside. MRI machines utilize a magnetic field to rearrange the water molecules in a person’s body to make it easier to produce cross-sectional and even 3D images of tissues, organs, and bones without an invasive procedure.
To enhance the clarity of MRI images, a doctor may order the use of an MRI contrasting agent. Gadolinium is one substance that is highly used as a contrasting agent for an MRI. Gadolinium is a chemical element that ordinarily appears in nature as a silver-white metal. To create an MRI contrast, gadolinium is combined with a chelating agent that is supposed to decrease the toxicity levels of gadolinium.
Prior to the administration of a gadolinium contrasting agent, a medical practitioner should ask about any medical conditions that could interact poorly with the contrasting agent. For example, if a patient has a kidney disease or had a previous allergic reaction to gadolinium, the substance should not be administered.
Gadolinium contrasting agents are administered through intravenous injections by a nurse or radiology technician. Ideally, a patient should pass the majority of the gadolinium injection through their urine within 24 hours of the injection. However, some patients may retain a substantial amount of gadolinium in their bloodstream. As a result, the substance will begin to poison the patient and possibly cause the development of other serious illnesses.

Signs and Symptoms of Gadolinium Poisoning:
Toxicity is a side effect of GBCAs that can occur within hours after undergoing an MRI scan with one of these contrast agents. Or it can manifest years later in people who have gadolinium buildup in their bodies.
*Temporary Side Effects
When a patient is administered gadolinium contrast, the patient may experience a number of temporary side effects. For example, a patient may feel a slight burning sensation in their veins after the injection.
Symptoms vary from person to person. The severity ranges from mild to severe.
Symptoms include:
Pain in the bones or joints
Burning or “pins and needle” sensations in the skin
Brain fog
Headache
Vision or hearing changes
Changes to the skin, such as thickening or discoloration
Nausea, vomiting, or diarrhea
Difficulty breathing
Flu-like symptoms
Metallic taste
*Allergic Reactions
Occasionally, a patient may develop a rash at the injection site soon after gadolinium contrasting agent has been administered. This type of reaction is usually indicative of a patient’s susceptibility to a more serious reaction. For instance, some patients may enter anaphylactic shock after receiving gadolinium contrast, which could result in a severe drop in blood pressure or even the restriction of airways.
*Kidney Interactions
A danger of gadolinium contrasting agents is the potential to negatively interact with a patient that has a pre-existing kidney function condition. If a patient with a prior kidney condition is administered gadolinium contrast, they could develop nephrogenic systemic fibrosis (NSF). NSF is a disease that causes a person to experience the contracting of skin, thickening of layers of skin, and severe organ damage.

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