Comparative Ochratoxin Toxicity: A Review of the Available Data

Abstract

Ochratoxins are a group of mycotoxins produced by a variety of moulds. Ochratoxin A (OTA), the most prominent member of this toxin family, was first described by van der Merwe et al. in Nature in 1965. Dietary exposure to OTA represents a serious health issue and has been associated with several human and animal diseases including poultry ochratoxicosis, porcine nephropathy, human endemic nephropathies and urinary tract tumours in humans. More than 30 years ago, OTA was shown to be carcinogenic in rodents and since then extensive research has been performed in order to investigate its mode of action, however, this is still under debate. OTA is regarded as the most toxic family member, however, other ochratoxins or their metabolites and, in particular, ochratoxin mixtures or combinations with other mycotoxins may represent serious threats to human and animal health. This review summarises and evaluates current knowledge about the differential and comparative toxicity of the ochratoxin group.

Keywords: biosynthesis; comparative toxicity; detection; metabolites; ochratoxin.

Figure 1

Overview of ochratoxin A (OTA) metabolites in animals and humans. Ochratoxins are differentially metabolised in various animals and humans depending on the metabolising enzymes present in liver, kidneys and/or gut. OTA, ochratoxin A; OTB, ochratoxin B; OTC, ochratoxin C; OTα, ochratoxin α; OTβ, ochratoxin β, OTHQ, OT hydroquinone; 4R-OH-OTB, 4R-hydroxyochratoxin B; OP-OTA, lactone-opened OTA; 10-OH-OTA, 10-hydroxyochratoxin A; 4R-OH-OTA, 4R-hydroxyochratoxin A; 4S-OH-OTA, 4S-hydroxyochratoxin A; 4S-OH-OTB, 4S-hydroxyochratoxin B. The respective metabolite is the main metabolite in the underlined taxa (for rodents, data of different authors is contradictory). Genera in brackets represent those where the metabolite has been detected, although it may be present in other animals or humans as well. Summarised from [52,53,92].

Figure 2

Comparison of cellular uptake of [³H]OTA and [³H]OTB. PKC, primary porcine kidney cells (male); HKC, primary human kidney cells (male). Columns represent means from at least three independent replicates ± SEM; modified from O’Brien et al. with permission [169].