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.
Images library
-
Title
Legend
-
25/04/90 After itraconazole treatment. Major improvement, defined as a complete response, after 10 weeks therapy with itraconazole.
-
Image A. Chest x-ray shows a single nodule in the left mid lung field.
Image B. This emphasises how chest x-rays in this context underestimate the extent of disease. The most anterior nodule has ground glass surrrounding the nodule, a halo sign. This diagnostic feature is missed on plain chest X-rays.
, 
-
Chest X ray after 4 days, prior to treatment, showing massive increase in volume of lesion (Fig 2)
-
Image A. This patient, aged 25 years developed a non productive cough and dyspnoea in the context of late-stage AIDS, CMV disease with ganciclovir-induced neutropenia and receiving corticosteroids. His chest radiograph shows fine bilateral reticular lower-lobe shadowing. He then developed gastro-intestinal bleeding with a gastric ulcer which showed hyphae on biopsy. He then developed blindness of one eye and the globe of his eye perforated. Hyphae were seen and Aspergillus cultured from the vitreous aspirate.
Image B. This radiograph, taken 25 days after the first and 3 days before death, shows of fine bilateral lower-lobe reticular shadows progressing to nodules in all lung zones.
This patient was reported as patient 3 in Denning DW, Follansbee S, Scolaro M, Norris S, Edelstein D, Stevens DA. Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324: 654-662.
, 
-
Further details
Image A. Bronchoscopy revealed Aspergillus on culture.
Image B. The ability of Aspergillus to cause pulmonary infarction, probably through direct angioinvasion in this case, is characteristic.
, 
-
(Fig 1) Chest radiograph with ‘classical’ appearance of a pulmonary infarction – a wedge-shaped lesion peripherally set against the pleura.
-
Large soft left upper-lobe shadow of focal invasive pulmonary aspergillosis in leukaemia, that was missed on earlier radiographs but apparent retrospectively. Variable density of the lesion suggests cavitation, which would be clearly visible on a CT scan of the thorax.
-
Severe unilateral invasive aspergillosis of the left lung, with complete consolidation of the left lower-lobe and reticular shadowing extending up into the left upper lobe. The right lung appears normal.
