[Alternia toxins as a health threat: cytotoxic effects]

Alternaria toxins are metabolites of fungi of the genus Alternaria that pose a potential health hazard. With the advent of modern analytical methods, they have begun to be detected in both raw materials and processed food. Despite the potential health risks, the content of Alternaria toxins in food is not regulated, and a lot of them remain completely unstudied. The aim of this review was to analyze and summarize the results of studies devoted to the investigation of the cytotoxic effects of Alternaria toxins via in vitro and in vivo experiments.

The search for sources was conducted in databases of peerreviewed scientific literature PubMed, Google Scholar and Cyberleninka without restrictions on year of publication by key words: Alternaria, Alternaria toxins, cytotoxicity, oxidative stress, toxicity.

The summarizing and analysis of data from studies on cytotoxicity, including DNA damage and oxidative stress (OS), and the results of toxicological experiments for the following metabolites of fungi of the genus Alternaria were carried out: alternariol (AOH), its monomethyl ether (AME), altenuene (ALT), tenuazonic acid (TeA), tentoxin (TEN), altertoxin I (ATX I), altertoxin II (ATX II), altertoxin III (ATX III), alterperinol (ALTP), stemphyltoxin III (STTX III). Dose-dependent death of healthy and cancer cells in many studies proves the high toxicological hazard of AOH. A part of the cell lines viability reduction has a negative impact on some tissues and organs to AME. Toxicity of ALT was contradictory, and TEN did not produce cytotoxic effects at concentrations below 100 μM. TeA in the concentration range of 109 to 187.6 μM caused 50% cancer cells death. The data for ATX I are contradictory, while ATX II, ATX III, STTX III and ALTP perylenequinones showed high cytotoxicity, due to the presence of epoxy groups. Mixtures of Alternaria toxins exhibit additive and synergistic effects, pose a hazard and require further investigation in new combinatorial studies. AOH and AME caused DNA damage, so additional data of genotoxicity in vivo are needed, focusing on the gastrointestinal tract. AOH, AME, and TeA are able to induce OS. There are no publications currently available to assess impact of ALT, TEN, and perylenequinones on OS parameters. Particular attention should be paid to perylenequinones due to their strong in vitro cytotoxicity.

Currently, sufficient data is available to confirm a health hazard only for AOH, and further data are needed for the remaining Alternaria fungal toxins.