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

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dc.contributor.authorOlaniyi, Kehinde
dc.contributor.authorAreloegbe, Stephanie
dc.contributor.authorAreola, Emmanuel
dc.contributor.authorSabinari, Isaiah
dc.contributor.authorFafure, Adedamola
dc.contributor.authorAgbana, Richard
dc.contributor.authorAtuma, Chukwubueze
dc.contributor.authorul haq Shah, Mohd Zahoor
dc.contributor.authorAjadi, Isaac
dc.contributor.authorOlatunji, Lawrence
dc.date.accessioned2025-05-09T15:12:14Z
dc.date.available2025-05-09T15:12:14Z
dc.date.issued2023-06-13
dc.description.abstractPolycystic 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. Interest ingly, 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.
dc.description.sponsorshipThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
dc.identifier.citationOlaniyi, K. S., Areloegbe, S. E., Areola, E. D., Sabinari, I. W., Fafure, A. A., Agbana, R. D., Atuma, C. L., Shah, M. Z. U. H., Ajadi, I. O., & Olatunji, L. A. (2023). Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome. Toxicology and Applied Pharmacology. 473, 116604, Published by Elsevier. Available online at: https://www.sciencedirect.com/journal/toxicology-and-applied-pharmacology/vol/473/suppl/C
dc.identifier.uri10.1016/j.taap.2023.116604
dc.identifier.urihttps://uilspace.unilorin.edu.ng/handle/123456789/16571
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofseries473; 116604
dc.subjectLow dose spironolactone
dc.subjectDyslipidemia
dc.subjectLiver
dc.subjectPCSK9
dc.subjectPCOS
dc.titleLow-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome
dc.typeArticle

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