The 8+ Benefits Of Deferoxamine

Deferoxamine Protects The Brain In Inflammation

Deferoxamine is a powerful drug that has many potential benefits in restoring neuronal health in those with stroke, Alzheimer's Disease, Parkinson's Disease, spinal cord injury.

In this post, I've gone through its potential benefits and natural alternatives to this drug. 

 
 

Basics

Deferoxamine (DFO) is a FDA-approved iron chelator. R

It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a healthcare system. R

It is normally used in iron overdose, in diseases with excess iron in the blood (either due to multiple blood transfusions or an underlying genetic condition), and patients with aluminium toxicity. R

New research on DFO has shown it to have many benefits in an iron-overloaded body through newly discovered mechanisms.

It works on protecting many organs against high iron including: 

  • Brain R
  • Heart R
  • Kidneys R
  • Liver R

Benefits of Deferoxamine

1. Reduces Neuroinflammation

 
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In the brain, DFO can reduce neuroinflammation (inflammation in the brain and central nervous system) by decreasing free radicals, microglial activation, and pro-inflammatory cytokines. R R R R

For example, DFO can protect against postoperative cognitive dysfunction (POCD) by decreasing microglia stress in the hippocampus. R

DFO when taken intramuscularly can help against the progression of Alzheimer's Disease (AD) and dementia. R

When taken intranasally, DFO may help reduce amyloid beta precursor protein (APP, a protein that contributes to AD), and improve memory in AD patients. R R

DFO can also decrease tau phosphorylation (another problem seen in AD). R

In Parkinson's Disease (PD), DFO may protect dopaminergic neurons from neurotoxicity from brain cell stressors such as iron, 6-OHDA, or MPTP. R

In PD, it may be taken intranasally to increase the production of dopamine in the substantia nigra (the part of the brain in PD that has dopaminergic loss). R R

DFO may also prevent a-synuclein (a biomarker in PD) accumulation and aggregation in PD. R R

DFO can also reduce iron load in nerve tissue while protecting neurons. R

For example, DFO given to spinal cord injury rats prevented scarring of the central nervous system, reduced lesion size, and increased the healing of rate astroglial cells. R

DFO can also protect brain cells against iron-induced damage in Huntington's Disease (HD). R

DFO may also protect the brain against the oxidative stress from sleep deprivation.

For example, bipolar rodent models that were given DFO and N-Acetyl-L-Cysteine (NAC) were able to mitigate manic symptoms after being exposed to sleep deprivation. R

DFO and NAC were also able to mitigate the neurotoxic effects of amphetamines in rodent models of attention deficit hyperactivity disorder (ADHD). R 

2. May Protect The Brain During Stroke

During subarachnoid hemorrhagic stroke (SAH), DFO may reduce hemorrhaging by 50%, while increasing the chances of a better outcome and faster recovery. R R R R 

For example, DFO can alleviate hydrocephalus (excess fluid in the brain). R

Also, during stroke DFO can stabilize the blood brain barrier (BBB), decrease the damage from iron overload, improve spacial memory, reduce neuronal death and stroke-induced damage size. R R R R R

It may also prevent seizures after SAH. R

During a stroke, there is less oxygen available to cells. R

DFO can increase hypoxia factor 1 (HIF1-alpha) which can help stabilize mitochondrial and cellular function during times without oxygen. R

DFO also protects astrocytes from glucose depletion during stroke. R

3. May Help With Wound, Bone, And Muscle Healing

DFO can increase wound healing. R R

When combined with stem cells, DFO can enhance wound healing even more. R R

DFO may helping heal venous leg ulcers, diabetic foot ulcers, and pressure ulcers. R R R

In patients with osteoarthritis, DFO can enhance collagen synthesis, cartilage healing and fracture healing. R R

DFO may also help with the regrowth of bones and may be beneficial in osteoporosis. R R

For example, DFO can also improve distraction osteogenesis (a reconstructive technique for bone growth and repair). R

In cultures resembling Duchenne muscular dystrophy (DMD), DFO with NAC can reduce stress in muscles. R

4. May Protect The Liver

DFO can decrease fat accumulation in non-alcoholic fatty liver disease (NAFLD) and iron-induced inflammation in the liver. R R R

By increasing HIF-1alpha expression, DFO improves glucose uptake, and increase insulin receptor activity and signaling in liver cells. R

DFO helps the liver maintain high levels of antioxidants and decreases scarring of the liver. R R

This protective effect is even more effective when DFO is combined with milk thistle. R

DFO is beneficial in protecting the liver in myelodysplastic syndromes. R

5. May Help With Obesity

In mice that were obese, DFO helped reduce weight grain. R

DFO also increases the production of brown fat and helps mitochondrial function in fatty tissue. R

DFO may also help with fat grafting. R

It may also helpful for diabetic neuropathy. R

6. May Protect The Kidneys

In a double blind study, NAC combined with DFO was effective in decreasing the severity and duration of acute kidney injury (AKI). R

DFO can also prevent scarring of the kidneys from iron overload. R

In patients with end-stage renal disease, DFO can protect against insulin resistance. R

7. May Protect The Vascular System

 
 

DFO may protect against iron-induced heart disease and increase long-term survival of the heart. R R R

For example, the combination NAC and DFO may improve the outcome of a heart attack. R

DFO may also protect against the detrimental effects of diabetes and insulin resistance on the heart. R

It may also help with age-related vascular problems. R

In patients with excess iron, DFO helps with sexual abnormalities and proper human development. R

For example, in patients with β-thalassemias (inherited blood disorders needing blood transfusions), DFO is major medicine used treat the iron overload caused by blood transfusion. R R

It may also help with sporadic porphyria cutanea tarda (PCT). R

In the lungs, DFO can improve the formation of alveoli and blood flow to the lungs. R R

8. May Protect Against Radiation

DFO may protect against some of the harms of high temperatures or electromagnetic fields (EMFs).

For example, in newborn rats exposed to high temperatures, DFO was able to help them maintain normal levels of natural antioxidants. R

It may protect the brain against EMF exposure by stabilizing glutathione and Vitamin E levels. R

DFO may also protect bones against the deleterious effects of radiotherapy. R R

Contrastingly, chicken hearts that were exposed to EMFs while treated with DFO had a worse ability to create new blood cells. R

Caveats

DFO may cause:

  • Abdominal pain, diarrhea, nausea, vomiting and hypotension (acutely) R
  • Cancer (growth in preexisiting cancer cells, has synergistic effects with arsenic) R R R R R
  • High levels of aminotransferase (AST), but is rare R
  • Retinopathy R R
  • Sepsis (in patients with Sickle Cell Anemia) R
  • Visual and auditory neurotoxicity (chronic treatment) R

High doses of DFO can increase blood pressure in the lungs. R

DFO therapy increases the risk of infection of MRSA, mucormycosis, pneumonia, vibrio and yersinia. R R R

It is unclear if the use of DFO during pregnancy or breastfeeding is safe. R

Natural Alternatives To Deferoxamine

 
 

Here are some other natural iron chelators that have similar properties to DFO:

Mechanism Of Action

Simple:

  • Increases AMPK R
  • Increases BDNF R
  • Increases COL2A1 R
  • Increases Dopamine R
  • Increases DMT1 R
  • Increases GDNF R
  • Increases HDL-C R
  • Increases HIF-1 R R R
  • Increases HO-1 R
  • Increases IL-8 (addition of NAC inhibits this increase) R R R
  • Increases IL-10 R
  • Increases LDL-C R R
  • Increases MDH2 R
  • Increases OGDC R
  • Increases pAkt-1 R
  • Increases PGC1-alpha R
  • Increases PLGF R
  • Increases PPAR-gamma R
  • Increases SDF-1α R R
  • Increases SDH R
  • Increases TCA R
  • Increases TGF-B (during cancer, but decreases in liver fibrosis) R R
  • Increases TH R
  • Increases TFR R
  • Increases UCP1 R
  • Increases VEGF R R
  • Inhibits p38 MAPK R
  • Inhibits XDH R
  • Decreases Caspase-3 R
  • Decreases Ferritin R
  • Decreases Fpn R
  • Decreases Gp91phox R
  • Decreases IL-1b R
  • Decreases IL-2 R
  • Decreases IL-6 R
  • Decreases LCN-2 R
  • Decreases MDA R
  • Decreases MMP-1 R
  • Decreases MMP-9 R
  • Decreases MMP-13 R
  • Decrease NO R
  • Decreases OX-42 R
  • Decreases ROS (opposite in cancer) R R
  • Decreases TNF-alpha R
  • Decreases Total Cholesterol R
  • Decreases Triglycerides R

Advanced:

  • DFO can be taken orally, topically, intramuscularly, intravenously, or intranasally. R R
  • DFO is a siderophore (meaning it comes from the bacteria Streptomyces pilosus) hexadentate chelator also known as Deferrioxamine B, Deferoxamine B, DFO-B, DFOA, DFB or desferal, DFXr, binding iron at a 1:1 molar ratio and binds to zinc, copper, and aluminium to a lesser extent. R R R R R
  • Old RBC iron storage will be released by reticuloendothelial system macrophages and precipitated by DFO and rapidly excreted through urine. R
  • Non-bonded DFO will be internalized by liver parenchymal cells and attached to excess hepatic iron and excreted via bile. R
  • DFO can directly absorb iron accumulation in cardiac muscle cells. R
  • One way it prevents toxicity in cells is by inhibiting hydroxyl radical synthesis. R
  • It crosses the blood brain barrier (BBB), but appears to be cross poorly when taken orally. R R
  • In the brain, DFO downregulated levels of gp91phox, the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase subunits which are participated in oxidative stress signaling. R
  • DFO also inhibits activation of p38 MAPK, thus decreasing neuroinflammation. R
  • DFO helps keep iron homeostasis in the hippocampus after trauma. R
  • After stroke, DFO is most efficacious in reducing brain edema when administered 2–4 hours after the induction of ICH, and this beneficial effect remained for up to 24 hours postinjury. R
  • In SAH models, DFO protects the BBB by increasing occluding, ZO-1 and claudin-5, and decreasing tight junction proteins. R
  • When hippocampal cells were triggered by lipopolysaccharide (LPS), DFO could preserve brain derived neurotrophic factor (BDNF) levels. R
  • In PD, DFO up-regulated the expression of HIF-1α protein, tyrosine hydroxylase (TH) and the survival of TH-positive neurons, vascular endothelial growth factor (VEGF), and growth associated protein 43 (GAP43) and down-regulated the expression of α-synuclein, divalent metal transporter with iron-responsive element (DMT1+IRE), and transferrin receptor (TFR). R R
  • In stem cells (adipose tissue or periodontal ligament) DFO increases VEGF, nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), neurotrophin-3 (NT3), IL-4 and IL-5. R R R
  • In the liver, DFO can improve hepatic steatosis by upregulating lipid metabolism (increase glucose uptake and improve insulin sensitivity), reduce reactive oxygen species (ROS), malodialdehyde (MDA), and proinflammatory cytokines, as well as the increase of hypoxia-inducible factor-1α pathway proteins and Bcl2/Bax ratio. R R
  • For example, DFO decreases in fasting serum insulin, B-cell function, glucose, HbA1c% and HOMA-IR. R
  • In patients with OA, DFO upregulated malate dehydrogenase (MDH2) gene expression and succinate dehydrogenase (SDH). R
  • Also in wound healing, DFO improve angiogenesis (via upregulation of VEGF and HIF1a). R 
  • DFO increases expression of histone deacetylase 9 (HDAC9), suppresses expression of K(lysine) acetyltransferase 5 (KAT5), and downregulates DNA methyltransferase 3A (DNMT3A), the enzyme that carries out genome-wide de novo DNA methylation. R
  • In the lungs, DFO enhances production of the angiogenic factors, placental growth factor (PLGF) and stromal cell-derived factor (SDF)-1. R

More Research

  • In cancer cells DFO inhibits the beneficial properties of artemisinin against cancer. R