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Oleic acid induces mitochondrial-mediated cell death via mPT pore and protects against estradiol benzoate-induced endometrial hyperplasia in female Wistar rats

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Abstract

Endometrial hyperplasia (EH) is a female gynecological disorder which occurs in women of reproductive age. It has been attributed to excessive exposure to estrogen and this has been linked to a loss of apoptotic signaling, thereby leading to malignancy. The available treatment options are quite expensive and associated with some side effects, thus; a need for better therapy. Oleic acid(OA) has been reported to have anticancer properties in some cancer cells. However, this study investigated its effect on mitochondrial-mediated cell death via mPT pore and estradiol benzoate (EB)-induced EH using rat model. Forty-six virgin female Wistar strain rats weighing between 180-200 g (7 weeks old) were used for this study. Mitochondria were isolated by differential centrifugation and exposed to different concentrations of OA. The mPT pore opening, cytochrome c release (CCR) and mitochondrial ATPase (mATPase) activity were assessed spectrophotometrically. Thirty-six female rats were equally grouped into six: A(Control), B(OA: 10 mg/kg), C(OA: 30 mg/kg), D(EB):(2 mg/kg), E(EB + OA 10 mg/kg) and F(EB + OA 30 mg/kg). The rats were orally treated for twelve weeks except for EB which was by intra-peritoneal injection. The cholesterol, estradiol, follicle-stimulating hormones, luteinizing hormones, malondialdehyde, superoxide dismutase, reduced glutathione, Interleukin-1β, Interleukin-6, Tumor Necrosis Factor alpha, and Interleukin-10β were determined using ELISA kits. Histological assessment of the uterine sections was determined. Oleic acid effected significant induction of mPT pore opening, CCR and mATPase activity. The cholesterol, sex hormones and inflammatory cytokines levels were significantly increased in the EB-treated group, which were remarkably reduced by OA treatment. The antioxidant indices were also restored by OA. Histology revealed severe EH and abundant deposition of collagens in the EB-treated group, which were attenuated by OA treatment. Treatment with OA mitigated the induced hyperplasia and reduced the collagen deposition. This study suggests antiproliferative potentials of OA in EB-induced EH as it induces mitochondrial-mediated cell death and protects against EB-induced EH in female Wistar rats.

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Authors and Affiliations

  1. Laboratory for Membrane Biochemistry Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Adeola Oluwakemi Olowofolahan & Olufunso Olabode Olorunsogo

  2. Department of Veterinary Anatomy, University of Ibadan, Ibadan, Nigeria

    Oluwasanmi Olayinka Aina

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  1. Adeola Oluwakemi Olowofolahan
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  2. Oluwasanmi Olayinka Aina
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Contributions

A.O. conceived the idea, designed the study and prepared the materials. A.O. and O.A. carried out the investigation, and collected the data. A.O. performed the statistical analyses. The first draft of the manuscript was written by A.O. and corrected by O.O. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Adeola Oluwakemi Olowofolahan.

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The experiment was carried out according to the rules and regulations for experimental animal management as stated in the Guide for the Care and Use of Laboratory. Animals (National Institute of Health (National Research Council (US) 2011).

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Olowofolahan, A.O., Aina, O.O. & Olorunsogo, O.O. Oleic acid induces mitochondrial-mediated cell death via mPT pore and protects against estradiol benzoate-induced endometrial hyperplasia in female Wistar rats. Comp Clin Pathol (2024). https://doi.org/10.1007/s00580-024-03577-3

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