Fungal toxins are considered secondary metabolites which may provide selective advantage under particular conditons.
Gliotoxin belongs to the epipolythiodioxopiperazine class of secondary metabolites (=ETPs).
The ETPs are produced by a wide variety of fungi, e.g., Aspergillus spp, Chaetomium spp, Penicillium spp, to mention a few. However, Gliotoxin produced by Aspergillus fumigatus has received wide attention because it is considered a virulence factor for A. fumigatus, as well as being present in the sera of cancer patients with aspergillosis (Sugui et al, 2007; Sugui et al, 2007; Bok et al, 2006).
Gliotoxin has been detected in the lung tissue and sera of mice with invasive aspergillosis and sera of cancer patients (Lewis et al, 2005a). The percentage of Aspergillus isolates from cancer patients produced gliotoxin as follows: fumigatus (93 %), niger (75 %), terreus (25 %) and flavus (4 %). (Lewis et al, 2005b). However, only 18 % of A. fumigatus in European patients produce gliotoxin, while 23 % of A. flavus isolates produced aflatoxin B1 (Kosalec and Pepeljnjak, 2005). The difference between the two reports may result from differences in strains of A. fumigatus in culture media and temperature (Kosalec et al, 2005).
The pathobiology of gliotoxin is multi-faceted (Kwon-Chung and Sugui, 2009). These are: 1) the S-S group in the ring forms adducts with cysteine residues of proteins; 2) The S-S group readily goes through a redox cycle production reactive oxygen species (ROS); 3) gliotoxin is immunosuppressive inhibiting phagocytosis; blocking NF-kB transcription factor, inhibiting proinflammatory response and cytokine production; 4) causes mitochondrial directed apoptosis ; 5) induces PM-mediated inflammation in organ transplant patients treated with corticosteroids.; and 6) the mycotoxin probably inhibits normal neutrophil functions in healthy subjects.
Finally, it was believed that gliotoxin was produced by the yeast Candida albicans. However, this observation has recently been questioned (Kupfahl et al 2007).
In conclusion, several species of Aspergillus and other fungi, as well as possibly yeast, produced gliotoxin both in vitro and in vivo. More attention should be paid to this mycotoxin because of its multi-faceted toxic properties.
What is Aspergillus?
Aspergillus spreads in the environment by releasing conidia which are capable of infiltrating the small alveolar airways of individuals.
In order to evade the body’s defenses Aspergillus releases Gliotoxin to inhibit the immune system (=prevent the immune system from reacting).
- Gliotoxin impairs the activation of T-cells. T-Cells are immune cells that protect the body from pathogens.
- Gliotoxin also induces apoptosis (=a form of programmed cell death) in monocytes (=a type of white blood cell) and in monocyte-derived dendritic cells (=T-cell helpers).
These impairments can lead to multiple neurological syndromes.
What is Invasive Aspergillosis?
Aspergillus fumigatus is responsible for a life-threatening systemic disease called “invasive aspergillosis” (IA) in immunocompromised individuals where mold actually grows inside the lungs but can invade other areas as well. Insufficient immune defense mechanisms result in high IA mortality rates in neutropenic (low white blood cell count) and immunosuppressed patients.
Connection to Multiple Sclerosis:
Recent research has implicated the mold produced immunosuppressive Gliotoxin as a likely cause of Multiple Sclerosis in people that have a genetic disposition for MS. The frequency of MS has been increasing. [L]
What is the standard treatment for mycotoxins in humans?
1. There is not a generally accepted “standard treatment.” There are many protocols developed by individual doctors who specialize in mold and mycotoxin associated illnesses. These include FIR Sauna, Glutathione, use of sequestering agents such as Cholestyramine or charcoal, antioxidants, probiotics, and intra-nasal anti-fungal treatments.
2. It is important to note that avoidance is the most important criteria. Leave the dwelling where you are being exposed until it is inspected by an Environmental Inspector and if necessary, remediated.
References:
http://www.ncbi.nlm.nih.gov/pubmed/19843884
http://www.ncbi.nlm.nih.gov/pubmed/17030582
http://www.ncbi.nlm.nih.gov/pubmed/20645385
http://www.ncbi.nlm.nih.gov/pubmed/15817772
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729542/
http://www.ncbi.nlm.nih.gov/pubmed/8777967
http://www.ncbi.nlm.nih.gov/pubmed/8666939
http://www.ncbi.nlm.nih.gov/pubmed/17626149
https://www.clinicaltherapeutics.com/article/S0149-2918(18)30189-9/pdf
https://globaljournals.org/GJMR_Volume14/1-Family-of-Six-their-Health.pdf
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