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Spironolactone reversed hepato-ovarian triglyceride accumulation caused by letrozole-induced polycystic ovarian syndrome: tissue uric acid—a familiar foe

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Abstract

Polycystic ovarian syndrome (PCOS) is a complex endocrine disease among women of reproductive age and is one of the main causes of infertility. Non-alcoholic fatty liver disease (NAFLD), the most prominent chronic liver disease in adults, is characterized by excess hepatic triglyceride (TG) accumulation. PCOS women have increased risk of NAFLD and uric acid has been documented to have a positive correlation with subclinical tissue damage and might be the link in the cystic. Spironolactone (SPL) is a mineralocorticoid receptor (MR) blocker that has been in wide clinical use for some decades. In this research, we investigated the effects of SPL on ovarian and hepatic tissue damage in experimental PCOS rats induced by letrozole (LET). A total of eighteen adult female Wistar rats were used for this study and the animals divided into 3 groups are treated with vehicle, LET (1 mg/kg), and LET+SPL (SPL; 0.25 mg/kg), p.o. once daily respectively for 21 uninterrupted days. Results showed that LET treatment induced features of PCOS characterized by increased plasma testosterone (T) and luteinizing hormone (LH) together with increased body weight. Abnormal ovarian and hepatic histomorphological changes were also observed with elevated uric acid (UA) and TG accumulation in both tissues respectively. Treatment with SPL however attenuated the elevated testosterone in the LET-induced PCOS model accompanied with a reversal in the observed ovarian and hepatic UA, TG accumulation, and altered histomorphological changes. Taken together, spironolactone reversed the PCOS-induced ovarian and hepatic tissue damage by suppressing tissue UA and TG accumulation.

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Acknowledgements

The authors acknowledge the technical support of Dr. Oniyide and Mrs. Olaiya Oluranti of Department of Physiology, Afe Babalola University. Mr. Adebowale of Bridge Biotech is also appreciated for the laboratory analysis.

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Authors and Affiliations

  1. Cardiometabolic Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, P.M.B. 5454, Ado-Ekiti, 360101, Nigeria

    Oluwaseun A. Adeyanju & Timothy O. Falodun

  2. HOPE Cardiometabolic Research Team & Department of Physiology, University of Ilorin, Ilorin, Nigeria

    Oluwaseun A. Adeyanju, Olugbenga S. Michael & Olaniyi A. Soetan

  3. Bioscience Research Hub, Ilorin, Kwara State, Nigeria

    Oluwaseun A. Adeyanju, Olugbenga S. Michael, Olaniyi A. Soetan & Aboyeji L. Oyewole

  4. Cardiometabolic Research Unit, Department of Physiology, College of Health sciences, Bowen University, Iwo, Nigeria

    Olugbenga S. Michael

  5. Department of Physiology, College of Medicine and Health Sciences, University of Ilorin, Ilorin, Nigeria

    Aboyeji L. Oyewole

  6. Department of Community Medicine, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria

    Richard D. Agbana

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  1. Oluwaseun A. Adeyanju
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Contributions

TOF was an undergraduate student under the supervision of OAA; OAA conceived and designed the experiments. OAA, TOF, and OSA conducted the experiments. OSM, ALO, and RDA contributed in statistical and data analyses. OAA and OSM both wrote the manuscript and OAA revised and edited the same. All authors read and approved the manuscript for publication.

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Correspondence to Oluwaseun A. Adeyanju.

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The investigation was conducted in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and was approved by the University ethical review committee, with protocol identification number NHREC29/10/2019, and every effort was made to minimize both the number of animals used and their sufferings.

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Adeyanju, O.A., Falodun, T.O., Michael, O.S. et al. Spironolactone reversed hepato-ovarian triglyceride accumulation caused by letrozole-induced polycystic ovarian syndrome: tissue uric acid—a familiar foe. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1055–1066 (2020). https://doi.org/10.1007/s00210-020-01809-1

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