Sex Hormones Differentially Modulate Ochratoxin A–Induced Nephrotoxicity in Female Rats

Ochratoxin A (OTA) is a nephrotoxic mycotoxin associated with renal tumour development, particularly in male rats. However, the influence of sex hormones on OTA toxicity in females remains unclear. This study investigated the roles of oestrogen and testosterone in modulating OTA nephrotoxicity in female Wistar rats. Four-month-old females (~220 g) were divided into four groups: intact (F-OTA), ovariectomized (F-OVA-OTA), testosterone-supplemented (F-OTA-Test) and antitestosterone-treated (F-OTA-Antitest). Animals received OTA (40 μg/rat/day, feed) for 9 or 24 weeks. Hormonal manipulations involved subcutaneous testosterone (625 μg/rat) or intramuscular antitestosterone (6.25 μg/rat) for 9 weeks. Plasma OTA concentrations were higher in intact (12.43 μg/mL) and antitestosterone (13.46 μg/mL) rats than in ovariectomized (9.67 μg/mL) or testosterone-supplemented (9.76 μg/mL) groups (p < 0.05). Renal histopathology scores (0-3) showed most severe lesions in testosterone-treated rats (2.71 ± 0.75), followed by ovariectomized (2.14 ± 0.69), intact (1.60 ± 0.54) and antitestosterone (1.00 ± 0.00) animals (p < 0.001). These findings demonstrate that oestrogen enhances OTA accumulation, whereas testosterone exacerbates renal damage. Conversely, blocking testosterone confers histological protection, suggesting a protective effect of oestrogen. Collectively, the results reveal a hormonal antagonism, with oestrogen and testosterone exerting opposing influences on OTA toxicodynamics, carrying important implications for sex-specific mycotoxin risk assessment.