Production of Citreoviridin, a Neurotoxic Mycotoxin of Penicillium Citreo-Viride Biourge

Abstract

In 1940, Miyake et al.¹ discovered toxic yellowed rice infected with a Penicillium sp. which was designated as P. toxicarium Miyake sp.var.² and later was identified as P. citreo-viride Biourge. Uraguchi^3,4,5,6 has carried out extensive toxicological and epidemiological investigations on the mouldy rice as a causative factor in acute cardiac beriberi (Shoshinkakke) which was prevalent in Japan in the past. He demonstrated that:

• (1) the ethanol extract of P. citreo-viride Biourge was actually neurotoxic to several animals, causing the same symptoms as those noted in acute cardiac beriberi;

• (2) a marked drop in the high incidence of ‘Shoshin-kakke’ in Japan occurred in 1910 although the discovery of vitamins occurred 1 year later and their usage in practical medicine only a further 10 years later, indicating that avitaminosis is not acceptable as a reasonable theory for the cause of ‘Shoshin-kakke’;

• (3) when rice inspection conducted by the Ministry of Agriculture was introduced in major rice-producing districts in about 1910 the high incidence of ‘Shoshin-kakke’ also decreased. Thus, intake of ungraded rice or mouldy rice is presumably a suspected causative factor in the disease.6 For these reasons Dr Uraguchi,^6,7,8 has stressed that acute cardiac beriberi is caused by mycotoxic intoxication originating from the metabolite(s) of P. citreo-viride Biourge.

This investigation was partly aided by the Grant for Cancer Research (1968–1969) from the Ministry of Welfare.