Date: 26 November 2013
Secondary metabolites, structure diagram: Trivial name – gliotoxin
Copyright: n/a
Notes:
Species: A. flavus, A. fumigatus, A. niger, A. terreus, Eurotium chevalieri, Neosartorya pseudofischeriSystematic name: 10H-3,10a-Epidithiopyrazino[1,2-a]indole-1,4-dione, 2,3,5a,6-tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-, (3R,5aS,6S,10aR)-Molecular formulae: C13H14N2O4S2Molecular weight: 326.393Chemical abstracts number: 67-99-2Selected references: Larsen TO, Smedsgaard J, Nielsen KF, Hansen MA, Samson RA, Frisvad JC. Production of mycotoxins by Aspergillus lentulus and other medically important and closely related species in section Fumigati. Med Mycol. 2007 May;45(3):225-32. Belkacemi, L.; Barton, R. C.; Hopwood, V.; Evans, E. G. V. (CORPORATE SOURCE PHLS Mycology Reference Laboratory, Department of Microbiology, University of Leeds, Leeds, UK). SOURCE Med. Mycol., 37(4), 227-233 (English) 1999 Blackwell Science Ltd. Lewis RE, Wiederhold NP, Lionakis MS, Prince RA, Kontoyiannis DP.J Clin Microbiol. 2005 Dec;43(12):6120-2. Frequency and species distribution of gliotoxin-producing Aspergillus isolates recovered from patients at a tertiary-care cancer center.Toxicity: Gliotoxin posseses a spectrum of biological activities including antibacterial and antiviral activities, and it is also a potent immunomodulating agent. Gliotoxin is also an inducer of apoptotic cell death in a number of cell types, and it has been found to be associated with some diseases attributed directly or indirectly to fungal infections. It is a secondary metabolite produced by a number of Aspergillus and Penicillium species.It is a potent immunosuppressive metabolite and brings about apoptosis in cells. Because of its effects on the immune system it may have a place in transplant surgery. There is limited evidence for its occurrence in moulded cereals. A. fumigatus is a potent pathogen which can colonise the lungs and other body tissues after ingestion of spores. There is some limited evidence that gliotoxin may be formed in situ in such circumstances. hamster LDLo oral 25mg/kg (25mg/kg) Veterinary and Human Toxicology. Vol. 32(Suppl), Pg. 63, 1990.mouse LD50 intraperitoneal 32mg/kg (32mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. mouse LD50 intravenous 7800ug/kg (7.8mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. mouse LD50 oral 67mg/kg (67mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. mouse LD50 subcutaneous 25mg/kg (25mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. rabbit LDLo intravenous 45mg/kg (45mg/kg) VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION. GASTROINTESTINAL: HYPERMOTILITY, DIARRHEA Journal of the American Chemical Society. Vol. 65, Pg. 2005, 1943. rat LDLo intravenous 45mg/kg (45mg/kg) Veterinary and Human Toxicology. Vol. 32(Suppl), Pg. 63, 1990.rat LDLo unreported 50mg/kg (50mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX) Journal of the American Chemical Society. Vol. 65, Pg. 2005, 1943.
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Pulmonary aspergillosis (K&E) (parrot C). Tissue from an individually housed and recently purchased, 6 month old African grey parrot found dead in the cage. Necropsy examination revealed focal necrosis of the left lung. This section stained by haematoxylin and eosin reveals septate fungal hyphae within the lung parenchyma. Similar hyphae were located in the walls and lumen of parabronchi, and within the walls of pulmonary blood vessels.
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Nasal aspergillosis. Tissue from an 8 year old, neutered male thoroughbred horse with an initial history of sinusitis leading to progressive neurological signs (ataxia, behavioural abnormalities) and prolonged recumbency. Necropsy examination revealed a focus of grey-caseous material within the right nasal chamber that comprised a mat of branching, septae fungal hyphae and mixed inflammatory cells (haematoxylin and eosin stain). Aspergillus spp was cultured from the lesion. There was no gross or histologica
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Immunofluorescence. Section of renal granuloma from dog J stained with polyclonal antiserum specific for Aspergillus terreus by immunofluorescence.
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Complement deposition (dog J). Section of myocardial granuloma from dog J stained for canine complement C3 by immunofluorescence. Deposition of C3, but not C4, on fungal hyphae suggests activation of the alternative rather than classical pathway of complement.
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Lymph node granuloma – Section of lymph node granuloma from a German shepherd dog with disseminated aspergillosis stained for canine IgA by immunofluorescence. The fungal hyphae within the centre of the lesion have surface IgA, and IgA-bearing plasma cells are present within the surrounding inflammatory infiltrate
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Extensive focus of pyogranulomatous inflammation within the kidney of dog J
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Aspergillus granuloma within the myocardium of dog J.
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Retinal aspergillosis (dog J) – Section of retina from a German shepherd dog with disseminated aspergillosis. Fungal hyphae and inflammatory cells are found within the vitreous
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Saggital section of kidney from a German shepherd dog with disseminated aspergillosis. There are granulomata within the medulla, and fungal material within the renal pelvis. Renal involvement in canine dissemianted aspergillosis is common, and the demonstration of fungal hyphae within urine sediment is a useful screening test.
