Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome
No Thumbnail Available
Date
2023-06-13
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
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. 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.
Description
Keywords
Low dose spironolactone, Dyslipidemia, Liver, PCSK9, PCOS
Citation
Olaniyi, 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