Cyclopiazonic acid: 50th anniversary of its discovery

In 1968, the mycotoxin cyclopiazonic acid (CPA) was first discovered and characterised as a chemical substance. Within the following five decades, much has been learned from the results of CPA research. CPA is produced by several Penicillium species (P. griseofulvum, P. camemberti, P. commune, P. dipodomyicola) and Aspergillus species (A. flavus, A. oryzae and A. tamarii). It is widespread on naturally contaminated agricultural raw materials. CPA has been reported to occur in food commodities (e.g. oilseeds, nuts, cereals, dried figs, milk, cheese and meat products) and to possess toxicological significance. CPA is also frequently detected in peanuts and maize; the presence of CPA and aflatoxins in maize and peanuts contaminated with A. flavus suggests that synergism may occur. CPA is toxic to several animal species, such as rats, pigs, guinea pigs, poultry and dogs. After ingesting CPA-contaminated feeds, test animals display severe gastrointestinal upsets and neurological disorders. Organs affected include the liver, kidney, heart, and digestive tract, which show degenerative changes and necrosis. Biologically, CPA is a specific inhibitor of sarco(endo) plasmic reticulum Ca2+-ATPase. Data from toxicological evaluation of aflatoxins and CPA in broiler chickens demonstrate that both aflatoxins and CPA alone and the aflatoxin-CPA combination can adversely affect broiler health. The effects of aflatoxins and CPA combination were additive in most cases.