The effects of orchidectomy on toxicological responses to dietary ochratoxin A in Wistar rats

Exp Toxicol Pathol. 2014 Aug;66(5-6):267-75. doi: 10.1016/j.etp.2014.04.002. Epub 2014 May 6.

Abstract

Ochratoxin A (OTA) causes pathological lesions in the organs of animals. Males are more sensitive to OTA exposure than females but the reasons for this are unknown. The objective of this study was to explore the role of testosterone in male rats with OTA-related pathogenesis. To test the effect of testosterone on OTA toxicity, the testes of a group of rats were surgically removed. Male and female rats (approximately 300 and 200 g) were fed with OTA-contaminated feed (initially approximately 300 μg kg(-1) b.w. per day) for 24 weeks. The organs of all the animals were collected and their organ lesion pathology, caspase-3 expression, OTA plasma and organ concentrations and total plasma testosterone concentrations were evaluated. OTA treatment created serious lesions in the kidney, liver and testes of rats. The major histopathological changes in the kidney and liver were karyomegaly, hemorrhages and vacuolization. In the testes, there was a marked decrease in the amount of spermatozoon. The degrees of organ lesion were evaluated and the castrated males had the lowest kidney and liver lesion scores, indicating that testosterone reduction in males dramatically reduces OTA-related organ damage. The plasma OTA levels for the intact males, the castrated and the females were 6.34, 8.42 and 12.5 μg ml(-1), respectively. In conclusion, despite the similar plasma OTA levels of the intact and castrated males, OTA is less toxic in the castrated males. Therefore, the well-known gender specific toxicity of OTA seems to be related to the testosterone levels of rats.

Keywords: Kidney; Ochratoxin A; Orchidectomy; Pathology; Testosterone; Toxicology; Wistar rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / biosynthesis
  • Female
  • Immunohistochemistry
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Ochratoxins / blood
  • Ochratoxins / pharmacokinetics
  • Ochratoxins / toxicity*
  • Orchiectomy*
  • Rats, Wistar
  • Sex Characteristics*
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology
  • Testis / surgery
  • Testosterone / blood
  • Testosterone / metabolism
  • Tissue Distribution
  • Toxicity Tests

Substances

  • Ochratoxins
  • ochratoxin A
  • Testosterone
  • Caspase 3