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3-(Para-fluorobenzoyl)-propionic acid; a metabolite of haloperidol, reversed oestradiol valerate-induced uterine hyperplasia via modulation of oestrogen receptor signalling pathways in female Wistar rats

Abstract Background 3-(Para-fluorobenzoyl)-propionic acid (3PFBPA) is one of the metabolites of haloperidol used in the treatment of psychotic disorders. 3PFBPA is an inhibitor of mitogen-activated protein kinase (MAPK), implicated in the development of uterine fibroids (UFs) and cellular proliferation. In this study, the effect of 3PFBPA on oestradiol valerate (OV)-induced uterine hyperplasia was investigated. Methods Uterine hyperplasia was induced by intraperitoneal (i.p.) injection of OV (3 mg/kg for 12 weeks). Expression of oestrogen receptor (ER) α, β-catenin and E-cadherin were investigated via immunohistochemistry. The histology and fibroblast cell count/μm2 (using histomorphometry) were carried out. Results There was a significant increase in the levels of oestrogen, progesterone and total cholesterol in the OV-treated group when compared with the control, assessed by enzyme-linked immunosorbent assay (ELISA) kits. Oestrogen and total cholesterol were markedly reduced in the OV + 3PFBPAtreated group when compared with the OV-treated group. The OV-induced overexpression of β-catenin and ER were also ameliorated by 3PFBPA. Also, the loss of E-cadherin function in the OV-treated group was restored by 3PFBPA. The histological findings and histomorphometric results revealed the presence of uterine hyperplasia in the OV-treated rats which was significantly reversed by 3PFBPA. Histological studies revealed a protective role against OV-induced uterine damage that was found after OV + 3PFBPA co-administration. Conclusion This study demonstrated that 3PFBPA ameliorates OV-induced uterine hyperplasia in the female Wistar rat model. The findings warrant further investigation of the antifibrotic effects of 3PFBPA in humans.