Background
Ochratoxin, a secondary metabolite produced by Aspergillus or Penicillium, widely contaminates agricultural products such as cereals, fruits and nuts, and feed, causing serious economic losses. Ochratoxins are nephrotoxic, hepatotoxic, enterotoxic, carcinogenic, teratogenic, and immunotoxic, posing a great threat to human and animal health. Ochratoxins contain ochratoxins A, B, and C, of which ochratoxin A (OTA) is the most prevalent and relevant mycotoxin.
In the chemical structures of all three toxins, the amino acid L-phenylalanine is linked by an amide bond to substituted dihydroisocoumaric acid. The chlorine substituent is the distinguishing feature of the OTA structure and correlates with the toxicity of OTA. The non-chlorinated form of OTA is ochratoxin B (OTB). OTA compounds are white, crystalline, and tasteless, with poor solubility in water but moderate solubility in polar organic solvents such as chloroform and ethanol. The carboxylic and phenolic hydroxyl groups in OTA can cause OTA to behave in different forms in aqueous solvents depending on the pH, including non-ionic, monoanionic (OTA-), and dianionic (OTA2-). Due to the isocoumarin molecule, OTA emits intense fluorescence upon absorption of UV light, which is significantly pH-dependent. OTA is rapidly absorbed and systemically distributed in humans and animals, but elimination and excretion are very slow, resulting in accumulation in the body. OTA is bound to plasma proteins and is poorly metabolized in vivo, with plasma half-lives ranging from a few days in rodents and pigs to several weeks in non-human primates and humans. It is metabolized primarily by hydrolysis to OTalpha, which is then bound to glucuronic acid.
Figure 1. Chemical structure of ochratoxin A, B, and C
(Source: EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), et al. 2020)
OTA is classified as a Group 2B carcinogen by the International Agency for Research on Cancer (IARC), and many countries limit its levels in agricultural foods. In the European Union, the Maximum Allowable Intake (MAI) for OTA is 3 μg/kg in cereals and cereal products, 2 μg/kg in wine and grape juice, and 0.5 μg/kg in foods for infants and young children. Preventing fungi from both infecting and producing mycotoxins is the most effective way to control mycotoxin contamination, but complete avoidance of fungal infections during plant growth is almost impossible to achieve, so more preventive measures are opting for removal of OTA contamination or detoxification of OTAs at the post-harvest or post-production stage.
Alternative Names
anti-Ochratoxin mAb
References
- 1. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), et al. Risk assessment of ochratoxin A in food. EFSA J. 2020 May 13;18(5):e06113.
- 2. Wang L, et al. Ochratoxin A: Occurrence and recent advances in detoxification. Toxicon. 2022 Apr 30;210:11-18.
References
Neurotoxicity of ochratoxin A: Molecular mechanisms and neurotherapeutic strategies
Toxicology
Authors: Obafemi BA, Adedara IA, Rocha JBT.
Abstract
Data from epidemiological and experimental studies have evidenced that some chemical contaminants in food elicit their harmful effects by targeting the central nervous system. Ochratoxin A is a foodborne mycotoxin produced by Aspergillus and Penicillium species. Research on neurotoxicity associated with ochratoxin A exposure has increased greatly in recent years. The present review accrued substantial evidence on the neurotoxicity associated with ochratoxin A exposure as well as discussed notable susceptible targets of noxious ochratoxin A at molecular, cellular and genetic levels. Specifically, the neurotoxic mechanisms associated with ochratoxin A exposure were unequivocally unraveled in vitro using human neuroblastoma SH-SY5Y cells, mouse hippocampal HT22 cells, human astrocyte (NHA-SV40LT) cells and microglia cells as well as in vivo using mammalian and non-mammalian models. Data from human biomonitoring studies on plasma ochratoxin A levels in patients with neurodegenerative diseases with some age- and sex-related responses were also highlighted. Moreover, the neurotherapeutic mechanisms of some naturally occurring bioactive compounds against ochratoxin A neurotoxicity are reviewed. Collectively, accumulated data from literature demonstrate that ochratoxin A is a neurotoxin with potential pathological involvement in neurological disorders. Cutting edge original translational research on the development of neurotherapeutics for neurotoxicity associated with foodborne toxicants including ochratoxin A is indispensable.
Corticosterone potentiates ochratoxin A-induced microglial activation
Biomol Concepts
Authors: Chansawhang A, Phochantachinda S, Temviriyanukul P, Chantong B.
Abstract
Microglial activation in the central nervous system (CNS) has been associated with brain damage and neurodegenerative disorders. Ochratoxin A (OTA) is a mycotoxin that occurs naturally in food and feed and has been associated with neurotoxicity, while corticosteroids are CNS' physiological function modulators. This study examined how OTA affected microglia activation and how corticosteroids influenced microglial neuroinflammation. Murine microglial cells (BV-2) were stimulated by OTA, and the potentiation effects on OTA-induced inflammation were determined by corticosterone pre-treatment. Expressions of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) were determined. Phosphorylation of mitogen-activated protein kinases (MAPKs) was analyzed by western blotting. OTA significantly increased the mRNA expression of IL-6, TNF-α, IL-1β, and iNOS and also elevated IL-6 and NO levels. Corticosterone pre-treatment enhanced the neuroinflammatory response to OTA in a mineralocorticoid receptor (MR)-dependent mechanism, which is associated with increases in extracellular signal-regulated kinase (ERK) and p38 MAPK activation. In response to OTA, microglial cells produced pro-inflammatory cytokines and NO, while corticosterone increased OTA-induced ERK and p38 MAPK phosphorylation via MR. Findings indicated the direct role of OTA in microglia activation and neuroinflammatory response and suggested that low corticosterone concentrations in the brain exacerbated neurodegeneration.