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Lethal effect of neutral mannan fraction of bakers' yeast in mice
Abstract:
A simple polysaccharide, the neutral mannan from Saccharomyces cerevisiae wild type strain (WNM) was found to kill ddY strain mice by intravenous administration, showing a LD50 value of 12.2 mg/kg. On the other hand, the acidic mannan fraction from the same yeast containing phosphate (WAM025), and chemically phosphorylated WNM (WNM-P) were practically non-toxic. Concerning the relationship between chemical structure and lethal effect of these mannans, it was demonstrated that a mannan possessing a highly branched structure exhibited stronger lethality than those with less branched structures. Against C3H/HeJ strain mice with no responsiveness to lipopolysaccharide, the LD50 value of WNM was as high as 75 mg/kg. Pretreatment with 500 mg/kg of D-mannose, N-acetyl-D-glucosamine, D-galactose, and L-fucose prevented mice from the lethal effects of WNM. However, WNM (LD100) did not show any lethal effect in mice for 2 to 12 hr after treatment with dexamethasone, an anti-inflammatory steroid.
Insights
Neutral mannan from Saccharomyces cerevisiae killed mice, but acidic or phosphorylated versions were non-toxic. Mannan lethality correlated with its branched structure, and toxicity was prevented by specific sugars or dexamethasone.
Area of Science:
- Immunology
- Biochemistry
- Toxicology
Background:
- Mannans are polysaccharides found in yeast cell walls.
- The toxicity of Saccharomyces cerevisiae mannan (WNM) varies based on its chemical structure and phosphorylation.
- Understanding mannan structure-toxicity relationships is crucial for potential therapeutic applications.
Purpose of the Study:
- To investigate the lethal effects of neutral mannan (WNM) from Saccharomyces cerevisiae.
- To determine the influence of mannan structure (branching, phosphorylation) on toxicity.
- To explore protective mechanisms against WNM-induced lethality.
Main Methods:
- Intravenous administration of WNM and its derivatives (WAM025, WNM-P) to ddY strain mice.
- Assessment of LD50 values for different mannan preparations.
- Evaluation of WNM toxicity in C3H/HeJ mice (lipopolysaccharide non-responsive).
- Pretreatment studies with various sugars and dexamethasone.
Main Results:
- Neutral mannan (WNM) exhibited significant lethality (LD50 = 12.2 mg/kg) in ddY mice.
- Acidic (WAM025) and phosphorylated (WNM-P) mannans were non-toxic.
- Highly branched mannans showed greater lethality.
- WNM toxicity was reduced in C3H/HeJ mice (LD50 = 75 mg/kg).
- Lethal effects were prevented by D-mannose, N-acetyl-D-glucosamine, D-galactose, and L-fucose.
- Dexamethasone pretreatment abolished WNM lethality.
Conclusions:
- The neutral mannan from Saccharomyces cerevisiae possesses significant toxicity, dependent on its structural branching.
- Phosphorylation and acidic modifications reduce or eliminate mannan toxicity.
- Specific monosaccharides and anti-inflammatory steroids can counteract mannan-induced lethality, suggesting immune-mediated mechanisms.