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BMC Endocrine Disorders
Published in: BMC Endocrine Disorders 1/2022

Open Access 01-12-2022 | Spironolactone | Research

Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model

Authors: Stephanie E. Areloegbe, Mmenyene U. Peter, Mosunmola B. Oyeleke, Kehinde S. Olaniyi

Published in: BMC Endocrine Disorders | Issue 1/2022

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Abstract

Background of study

Globally, many reproductive aged women are affected by polycystic ovarian syndrome (PCOS), which is a common endocrine and metabolic disorder that is linked with adipose dysfunction and chronic low-grade inflammation. Spironolactone (SPL), a mineralocorticoid receptor blocker has been documented as a metabolic modulator. However, its immunomodulatory effect in PCOS is unknown. Therefore, the present study hypothesized that SPL would ameliorate adipose dysfunction and inflammation in experimental PCOS animals.

Materials and methods

Female Wistar rats that were 8 weeks old were allocated into three groups. Group 1 received vehicle (distilled water; p.o.), group 2 received letrozole (1 mg/kg; p.o.) and group 3 received letrozole plus SPL (0.25 mg/kg, p.o.). The administration was performed once daily for 21 days.

Results

The experimental PCOS animals showed insulin resistance, hyperinsulinemia and hyperandrogenism as well as oxidative stress and elevated inflammatory biomarkers (NF-kB/TNF-/IL-6) as well as a significant decrease in triglycerides, total cholesterol, free fatty acids, GSH and G6PD in the adipose tissue of PCOS animals. In addition, immunohistochemical assessment of adipose tissue showed significant expression of BAX and inflammasome, indicating apoptosis and inflammation compared to control animals. Nevertheless, administration of SPL attenuated these perturbations.

Conclusion

Altogether, the present study suggests that low-dose spironolactone confers protection against adipose dysfunction in experimental PCOS animals by attenuating inflammation, oxidative stress and cellular apoptosis.
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Literature
1.
Kabel AM, Alghubayshi AY, Moharm FM. The impact of polycystic ovarian syndrome, a potential risk factor to endometrial cancer, on the quality of sleep. J Cancer Res Treat. 2016;4(6):96–8.
2.
Zafar U, Memon Z, Moin K, Agha S, Hassan JA, Zehra D. Prevalence of PCOS with associated symptoms and complications at tertiary care hospital of Karachi. J Adv Med Med Res. 2019;30(4):1–9.CrossRef
3.
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–9.CrossRefPubMed
4.
Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37(5):467–520.CrossRefPubMedPubMedCentral
5.
Kumarapeli VL, Seneviratne RD, Wijeyaratne CN. Health-related quality of life and psychological distress in polycystic ovary syndrome: a hidden facet in South Asian women. BJOG. 2011;118(3):319–28.CrossRefPubMed
6.
Yu Y, Tan P, Zhuang Z, Wang Z, Zhu L, Qiu R, Xu H. Untargeted metabolomic approach to study the serum metabolites in women with polycystic ovary syndrome. BMC Med Genomics. 2021;14(1):1–5.CrossRef
7.
Jones H, Sprung VS, Pugh CJ, Daousi C, Irwin A, Aziz N, Adams VL, Thomas EL, Bell JD, Kemp GJ, Cuthbertson DJ. Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J Clin Endocrinol Metab. 2012;97(10):3709–16.CrossRefPubMed
8.
Villa J, Pratley RE. Adipose tissue dysfunction in polycystic ovary syndrome. Curr DiabRep. 2011;11(3):179–84.
9.
Palomba S, Santagni S, Falbo A, La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Women’s Health. 2015;7:745.CrossRef
10.
Osibogun O, Ogunmoroti O, Michos ED. Polycystic ovary syndrome and cardiometabolic risk: opportunities for cardiovascular disease prevention. Trends Cardiovasc Med. 2020;30(7):399–404.CrossRefPubMed
11.
Lecke SB, Morsch DM, Spritzer PM. Association between adipose tissue expression and serum levels of leptin and adiponectin in women with polycystic ovary syndrome. Genet Mol Res. 2013;12(4):4292–6.CrossRefPubMed
12.
Shimobayashi M, Albert V, Woelnerhanssen B, Frei IC, Weissenberger D, Meyer-Gerspach AC, Clement N, Moes S, Colombi M, Meier JA, Swierczynska MM. Insulin resistance causes inflammation in adipose tissue. J Clin Investig. 2018;128(4):1538–50.CrossRefPubMedPubMedCentral
13.
Nishimura S, Manabe I, Nagasaki M, Hosoya Y, Yamashita H, Fujita H, Ohsugi M, Tobe K, Kadowaki T, Nagai R, Sugiura S. Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes. 2007;56(6):1517–26.CrossRefPubMed
14.
15.
Suganami T, Ogawa Y. Adipose tissue macrophages: their role in adipose tissue remodeling. J Leukoc Biol. 2010;88(1):33–9.CrossRefPubMed
16.
Yao L, Wang Q, Zhang R, Wang X, Liu Y, Di F, Song L, Xu S. Brown adipose transplantation improves polycystic ovary syndrome-involved metabolome remodeling. Front Endocrinol. 2021;12:747944.CrossRef
17.
Marzolla V, Armani A, Zennaro MC, Cinti F, Mammi C, Fabbri A, Rosano GM, Caprio M. The role of the mineralocorticoid receptor in adipocyte biology and fat metabolism. Mol Cell Endocrinol. 2012;350(2):281–8.CrossRefPubMed
18.
Feraco A, Marzolla V, Scuteri A, Armani A, Caprio M. Mineralocorticoid receptors in metabolic syndrome: from physiology to disease. Trends Endocrinol Metab. 2020;31(3):205–17.CrossRefPubMed
19.
Jia G, Aroor AR, Sowers JR. The role of mineralocorticoid receptor signaling in the cross-talk between adipose tissue and the vascular wall. Cardiovasc Res. 2017;113(9):1055–63.CrossRefPubMedPubMedCentral
20.
Danjuma MI, Mukherjee I, Makaronidis J, Osula S. Converging indications of aldosterone antagonists (spironolactone and eplerenone): a narrative review of safety profiles. Curr Hypertens Rep. 2014;16(2):1.CrossRef
21.
Thuzar M, Stowasser M. The mineralocorticoid receptor—an emerging player in metabolic syndrome? J Hum Hypertens. 2021;35(2):117–23.CrossRefPubMed
22.
Christy NA, Franks AS, Cross LB. Spironolactone for hirsutism in polycystic ovary syndrome. Ann Pharmacother. 2005;39(9):1517–21.CrossRefPubMed
23.
Armanini D, Andrisani A, Bordin L, Sabbadin C. Spironolactone in the treatment of polycystic ovary syndrome. Expert Opin Pharmacother. 2016;17(13):1713–5.CrossRefPubMed
24.
Sabbadin C, Andrisani A, Zermiani M, Donà G, Bordin L, Ragazzi E, Boscaro M, Ambrosini G, Armanini D. Spironolactone and intermenstrual bleeding in polycystic ovary syndrome with normal BMI. J Endocrinol Invest. 2016;39(9):1015–21.CrossRefPubMed
25.
Ganie MA, Khurana ML, Nisar S, Shah PA, Shah ZA, Kulshrestha B, Gupta N, Zargar MA, Wani TA, Mudasir S, Mir FA. Improved efficacy of low-dose spironolactone and metformin combination than either drug alone in the management of women with polycystic ovary syndrome (PCOS): a six-month, open-label randomized study. J Clin Endocrinol Metab. 2013;98(9):3599–607.CrossRefPubMed
26.
Mayyas FA, Aljohmani AI, Alzoubi KH. The impact of spironolactone on markers of myocardial oxidative status, inflammation and remodeling in hyperthyroid rats. Curr Mol Pharmacol. 2020;13(3):206–15.CrossRefPubMed
27.
Adeyanju OA, Falodun TO, Fabunmi OA, Olatunji LA, Soladoye AO. Very low dose spironolactone protects experimentally-induced polycystic ovarian syndrome from insulin-resistant metabolic disturbances by suppressing elevated circulating testosterone. Chem Biol Interact. 2019;310:108742.CrossRefPubMed
28.
Olaniyi KS, Oniyide AA, Adeyanju OA, Ojulari LS, Omoaghe AO, Olaiya OE. Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS. Toxicol Appl Pharmacol. 2021;15(411):115381.CrossRef
29.
Kafali H, Iriadam M, Ozardalı I, Demir N. Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res. 2004;35(2):103–8.CrossRefPubMed
30.
Olaniyi KS, Areloegbe SE. Suppression of PCSK9/NF-kB-dependent pathways by acetate ameliorates cardiac inflammation in a rat model of polycystic ovarian syndrome. Life Sci. 2022;300:120560.CrossRefPubMed
31.
Dangana EO, Omolekulo TE, Areola ED, Olaniyi KS, Soladoye AO, Olatunji LA. Sodium acetate protects against nicotine-induced excess hepatic lipid in male rats by suppressing xanthine oxidase activity. Chem Biol Interact. 2020;25(316):108929.CrossRef
32.
Zheng JY, Yang GS, Wang WZ, Li J, Li KZ, Guan WX, Wang WL. Overexpression of Bax induces apoptosis and enhances drug sensitivity of hepatocellular cancer-9204 cells. World J Gastroenterol: WJG. 2005;11(23):3498.CrossRefPubMedPubMedCentral
33.
Pisani C, Ramella M, Boldorini R, Loi G, Billia M, Boccafoschi F, Volpe A, Krengli M. Apoptotic and predictive factors by Bax, Caspases 3/9, Bcl-2, p53 and Ki-67 in prostate cancer after 12 Gy single-dose. Sci Rep. 2020;10(1):1.CrossRef
34.
Yu S, Yin JJ, Miao JX, Li SG, Huang CZ, Huang N, Fan TL, Li XN, Wang YH, Han SN, Zhang LR. Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma. Oncol Rep. 2020;43(4):1113–24.PubMedPubMedCentral
35.
Jamil AS, Alalaf SK, Al-Tawil NG, Al-Shawaf T. A case–control observational study of insulin resistance and metabolic syndrome among the four phenotypes of polycystic ovary syndrome based on Rotterdam criteria. Reprod Health. 2015;12(1):1–9.CrossRef
36.
González F, Rote NS, Minium J, Kirwan JP. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(1):336–40.CrossRefPubMed
37.
38.
Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015;36(5):487–525.CrossRefPubMedPubMedCentral
39.
Engin AB. Adipocyte-macrophage cross-talk in obesity. Obesity and lipotoxicity. 2017:327–43.
40.
Kim JJ, Choi YM. Dyslipidemia in women with polycystic ovary syndrome. Obstetrics & gynecology science. 2013;56(3):137–42.CrossRef
41.
Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol. 2010;11(10):936–44.CrossRefPubMed
42.
Deligeoroglou E, Vrachnis N, Athanasopoulos N, Iliodromiti Z, Sifakis S, Iliodromiti S, Siristatidis C, Creatsas G. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol Endocrinol. 2012;28(12):974–8.CrossRefPubMed
43.
44.
Hwang MH, Yoo JK, Luttrell M, Meade TH, English M, Christou DD. Effect of selective mineralocorticoid receptor blockade on flow-mediated dilation and insulin resistance in older adults with metabolic syndrome. Metab Syndr Relat Disord. 2015;13(8):356–61.CrossRefPubMedPubMedCentral
45.
Zuo T, Zhu M, Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxid Med Cell Longev. 2016;2016:8589318.CrossRefPubMed
46.
Zhao JV, Xu L, Lin SL, Schooling CM. Spironolactone and glucose metabolism, a systematic review and meta-analysis of randomized controlled trials. J Am Soc Hypertens. 2016;10(8):671–82.CrossRefPubMed
47.
Victorio JA, Clerici SP, Palacios R, Alonso MJ, Vassallo DV, Jaffe IZ, Rossoni LV, Davel AP. Spironolactone prevents endothelial nitric oxide synthase uncoupling and vascular dysfunction induced by β-adrenergic overstimulation: role of perivascular adipose tissue. Hypertension. 2016;68(3):726–35.CrossRefPubMed
48.
Olivier A, Pitt B, Girerd N, Lamiral Z, Machu JL, McMurray JJ, Swedberg K, van Veldhuisen DJ, Collier TJ, Pocock SJ, Rossignol P. Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity. Insight from the EMPHASIS-HF trial. Eur J Heart Fail. 2017;19(9):1186–97.CrossRefPubMed
Metadata
Title
Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model
Authors
Stephanie E. Areloegbe
Mmenyene U. Peter
Mosunmola B. Oyeleke
Kehinde S. Olaniyi
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2022
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-022-01143-y

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