Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome.

Autor: Olaniyi KS; Cardio/Endo-Metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria. Electronic address: olaniyisk@abuad.edu.ng., Areloegbe SE; Cardio/Endo-Metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria., Areola ED; Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria., Sabinari IW; Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria., Fafure AA; Neuroscience Unit, Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria., Agbana RD; Department of Community medicine, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria., Atuma CL; Cardio/Endo-Metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria., Shah MZUH; Laboratory of Endocrinology, Department of Bioscience, Barkatullah University Bhopal, Madhya Predesh 462026, India., Ajadi IO; Department of Physiology, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria., Olatunji LA; Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2023 Aug 15; Vol. 473, pp. 116604. Date of Electronic Publication: 2023 Jun 14.
DOI: 10.1016/j.taap.2023.116604
Abstrakt: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women and it is associated with overt metabolic derangement. Circulating lipids are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9) which blocks low density lipoprotein (LDL) receptors especially in the liver. The liver is highly vulnerable in dyslipidemia as lipid accumulation leads to progression of non-alcoholic fatty liver disease (NAFLD). An array of scientific endeavours hold that low-dose spironolactone (LDS) is beneficial as intervention for PCOS traits, but this claim is yet to be fully elucidated. The aim of this study was to investigate the effect of LDS on dyslipidemia and hepatic inflammation in rats with letrozole (LET)-induced PCOS and to assess the possible involvement of PCSK9 in these effects. Eighteen female Wistar rats were randomly assigned into 3 groups. The control group received vehicle (distilled water; p.o.), LET-treated group received letrozole (1 mg/kg; p.o.), LET+LDS-treated group received LET plus LDS (0.25 mg/kg, p.o.) for 21 days. Exposure to LET increased body and hepatic weights, plasma and hepatic total cholesterol (TC), TC/HDL, LDL, interleukin-6, MDA, PCSK9, ovarian degenerated follicles and hepatic NLRP3 intensity, reduced GSH and normal ovarian follicles. Interestingly, LDS averted dyslipidemia, NLRP3-dependent hepatic inflammation and ovarian PCOS traits. It is evident herein that LDS ameliorates PCOS traits and combats dyslipidemia and hepatic inflammation in PCOS by a PCSK9-dependent mechanism.
Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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