Elsevier

Biochemical Pharmacology

Volume 37, Issue 23, 1 December 1988, Pages 4469-4477
Biochemical Pharmacology

Research paper
Lipid peroxidation as a possible cause of ochratoxin a toxicity

https://doi.org/10.1016/0006-2952(88)90662-4Get rights and content

Abstract

Addition of the mycotoxin ochratoxin A (OA), a nephrotoxic carcinogen, to rat liver microsomes greatly enhanced the rate of NADPH or ascorbate-dependent lipid peroxidation as measured by malondialdehyde formation. NADPH-dependent lipid peroxidation in kidney microsomes was similarly enhanced by OA. The process required the presence of trace amounts of iron but cytochrome P-450 and free active oxygen species appeared not to be involved.

The efficiency of several ochratoxins (ochratoxins A, B, C, α and O-methyl-ochratoxin C) to enhance lipid peroxidation was related to the presence and reactivity of the phenolic hydroxyl group. Furthermore, the ability of these ochratoxins to enhance lipid peroxidation in microsomes correlated precisely with their known toxicities in chicks. Administration of ochratoxin A to rats also resulted in enhanced lipid peroxidation in vivo as evidenced by a seven-fold increase in the rate of ethane exhalation.

These results suggest that lipid peroxidation may play a role in the observed toxicity of ochratoxin A in animals; a mechanism is proposed.

References (45)

Cited by (181)

  • Aflatoxins, ochratoxins, and citrinin

    2022, Reproductive and Developmental Toxicology
  • Multiomics approach for mycotoxins toxicology

    2020, Food Toxicology and Forensics
  • Ochratoxin A: Toxicity, oxidative stress and metabolism

    2018, Food and Chemical Toxicology
    Citation Excerpt :

    OTA-enhanced lipid peroxidation affects the permeability of the plasma membrane to Ca2+ and thus impairs calcium homeostasis by enhancing Ca2+ influx, releasing it from intracellular stores and influencing calcium-sensitive channels. In the presence of NADPH-CYP450 reductase, OTA–Fe3+ complex facilitates the reduction of Fe3+, and the OTA–Fe2+ complex formed initiates the appearance of free radicals, leading to lipid peroxidation (Omar et al., 1990; Rahimtula et al., 1988). A significant increase in the levels of protein nitrotyrosine residues was observed with OTA, and it was also found that Nrf2 activators could prevent OTA-induced protein nitration.

View all citing articles on Scopus
View full text