Compendium of the most significant studies with reference to properties, intake, effects.

Urbain P, Valverde J, Jakobsen J. Impact on Vitamin D2, Vitamin D4 and Agaritine in Agaricus bisporus Mushrooms after Artificial and Natural Solar UV Light Exposure. Plant Foods Hum Nutr. 2016 Sep;71(3):314-21. doi: 10.1007/s11130-016-0562-5. 

Abstract. Commercial mushroom production can expose mushrooms post-harvest to UV light for purposes of vitamin D2 enrichment by converting the naturally occurring provitamin D2 (ergosterol). The objectives of the present study were to artificially simulate solar UV-B doses occurring naturally in Central Europe and to investigate vitamin D2 and vitamin D4 production in sliced Agaricus bisporus (button mushrooms) and to analyse and compare the agaritine content of naturally and artificially UV-irradiated mushrooms. Agaritine was measured for safety aspects even though there is no rationale for a link between UV light exposure and agaritine content. The artificial UV-B dose of 0.53 J/cm(2) raised the vitamin D2 content to significantly (P < 0.001) higher levels of 67.1 ± 9.9 μg/g dry weight (DW) than sun exposure (3.9 ± 0.8 μg/g dry DW). We observed a positive correlation between vitamin D4 and vitamin D2 production (r(2) = 0.96, P < 0.001) after artificial UV irradiation, with vitamin D4 levels ranging from 0 to 20.9 μg/g DW. The agaritine content varied widely but remained within normal ranges in all samples. Irrespective of the irradiation source, agaritine dropped dramatically in conjunction with all UV-B doses both artificial and natural solar, probably due to its known instability. The biological action of vitamin D from UV-exposed mushrooms reflects the activity of these two major vitamin D analogues (D2, D4). Vitamin D4 should be analysed and agaritine disregarded in future studies of UV-exposed mushrooms.

Merdivan S, Willke C, Lindequist U. Development and Validation of an LC-MS/MS Method for the Quantification of Agaritine in Mushrooms. Int J Med Mushrooms. 2016;18(1):13-21. doi: 10.1615/IntJMedMushrooms.v18.i1.30. 

Abstract. Agaritine, an aromatic hydrazine, is found as a secondary metabolite in mushroom species. It is among others suspected to exhibit genotoxic activity. This publication describes the validation of a method for the quantification of agaritine in mushrooms (i.e., extraction and purification by solid phase extraction) and measurement by liquid chromatography with tandem mass spectrometry detection in positive ionization mode. The results show this method to be selective, accurate, and precise. This method could be used for the quality control of pharmaceutical preparations containing mushrooms.

Schulzova V, Hajslova J, Peroutka R, Hlavasek J, Gry J, Andersson HC. Agaritine content of 53 Agaricus species collected from nature. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2009 Jan;26(1):82-93. doi: 10.1080/02652030802039903. 

Abstract. Fifty-three different species of the genus Agaricus were collected in the Czech Republic during the period 1998-2001 and identified by an experienced mycologist. The samples were analysed for agaritine (N2-(gamma-L-glutamyl)-4-hydroxymethylphenylhydrazine) content, a precursor to a suspected rodent carcinogen. There was a huge variation in agaritine content between species, but less variation between samples of a species. Whereas the cultivated mushroom Agaricus bisporus commonly contain 200-500 mg agaritine kg(-1) fresh weight, no less than 24 of the 53 species contained agaritine levels above 1000 mg kg(-1) fresh weight. The highest level was found in A. elvensis containing up to 10, 000 mg kg(-1) fresh weight. Twenty species contained intermediate levels (100-1000 mg kg(-1)), and nine species were below 100 mg kg(-1). Some of the species producing low levels of agaritine might be candidates for future strain development of Agaricus mushrooms for cultivation. No correlation could be observed between agaritine content and size of the mushroom, week of the year when collected, year of collection, or site of collection. Besides occurring in the genus Agaricus, some species of the genera Leucoagaricus and Macrolepiota were also shown to contain agaritine.

Sommer I, Schwartz H, Solar S, Sontag G. Effect of gamma-irradiation on agaritine, gamma-glutaminyl-4-hydroxybenzene (GHB), antioxidant capacity, and total phenolic content of mushrooms ( Agaricus bisporus ). J Agric Food Chem. 2009 Jul 8;57(13):5790-4. doi: 10.1021/jf900993h. 

Abstract. Fresh mushrooms ( Agaricus bisporus ) were irradiated at doses of 1, 3, and 5 kGy to assess the effect of gamma-irradiation on the major aromatic compounds agaritine (beta-N-(gamma-L-(+)-glutamyl)-4-(hydroxymethyl)phenylhydrazine) and GHB (gamma-glutaminyl-4-hydroxybenzene) as well as on the total phenolic content and antioxidant capacity. Up to 3 kGy, agaritine was not affected. At 5 kGy, a significant reduction (p = 0.05) from 1.54 (0 kGy) to 1.35 g/kg dry weight (DW) was observed. gamma-Glutaminyl-4-hydroxybenzene decreased by 22% at 1 kGy and by 31% at 5 kGy. Additionally, agaritine standard solutions at concentrations of 10(-4) and 5 x 10(-5) mol/L were irradiated to compare the effect on agaritine content in aqueous solutions and in the sample matrix. A rapid decay was observed, 50% at 750 Gy (10(-4) mol/L) and 400 Gy (5 x 10(-5) mol/L). The total phenolic content and antioxidant capacity were not significantly (p = 0.05) influenced by irradiation.

Kondo K, Watanabe A, Akiyama H, Maitani T. The metabolisms of agaritine, a mushroom hydrazine in mice. Food Chem Toxicol. 2008 Mar;46(3):854-62. doi: 10.1016/j.fct.2007.10.022.

Abstract. The mushroom hydrazine agaritine was measured in mouse plasma and urine using LC/MS/MS, which is highly specific. Agaritine concentration peaked 20 min after oral administration to mice (4.0 and 40 mg/kg). The concentration gradually decreased and returned to the basal level in 100 min. The maximum concentration, the time to the maximum concentration, and the half life were 0.37 microg/ml plasma, 0.33 h, and 0.71 h, respectively after administration of agaritine at 40 mg/kg body weight. One agaritine metabolite was found in the plasma and the urine from agaritine-administered mice. The structure of metabolites of agaritine by gamma-GT was next investigated using LC/MS. HMPH proved to be generated from agaritine. The oxidative stress marker 8-OHdG was detected in agaritine-administered mouse urine. After administration, the 8-OHdG level immediately tripled, and then decreased to the control level over 48 h. Its level then elevated again and remained high for 11 days. These results suggest that agaritine quickly metabolizes and disappears in the plasma, whereas DNA damage lasts for a long time after a single administration of agaritine to mice.