Is oxidative stress involved in the sex-dependent response to ochratoxin A renal toxicity?

José Manuel Enciso1, Adela López de Cerain2, Laura Pastor1

  • 1University of Navarra, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, c/Irunlarrea 1, 31008 Pamplona, Spain.

Insights

Ochratoxin A (OTA) does not cause sex-specific oxidative stress in rat kidneys. This study found no significant differences in oxidative stress markers between male and female rats exposed to OTA.

Area of Science:

  • Toxicology
  • Carcinogenesis
  • Oxidative Stress

Background:

  • Ochratoxin A (OTA) is a potent renal carcinogen in rodents and a possible human carcinogen.
  • Its carcinogenic mechanism is unclear, but oxidative stress and DNA damage are suspected contributors.
  • Previous studies noted significant sex differences in OTA carcinogenicity, with males being more susceptible.

Purpose of the Study:

  • To investigate potential sex differences in oxidative stress responses to Ochratoxin A (OTA) in rat kidneys.
  • To assess the role of oxidative stress in OTA-induced renal toxicity and carcinogenicity.

Main Methods:

  • Male and female F344 rats were administered OTA orally for 7 or 21 days.
  • Kidney tissues were analyzed for total glutathione (tGSH), oxidized glutathione (GSSG), glutathione S-transferase (GST), and superoxide dismutase (SOD) activity.
  • The alkaline comet assay with Formamidopyrimidine-DNA glycosylase (Fpg) was used to detect oxidized DNA bases.

Main Results:

  • No biologically relevant sex differences were observed in any of the oxidative stress-related parameters analyzed.
  • No significant oxidative stress response was detected in OTA-treated animals compared to controls.
  • These findings align with previous observations of similar OTA levels and histopathological changes between sexes.

Conclusions:

  • The study concludes that there are no sex-based differences in the oxidative stress response to Ochratoxin A in the kidneys of F344 rats.
  • These results suggest that oxidative stress may not be the primary mechanism driving the observed sex differences in OTA carcinogenicity.

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