Butyrate-Mediated Modulation of Paraoxonase-1 Alleviates Cardiorenometabolic Abnormalities in a Rat Model of Polycystic Ovarian Syndrome.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Drugs and Therapy Pub Date : 2024-11-16 DOI:10.1007/s10557-024-07649-y

Kehinde S Olaniyi, Stephanie E Areloegbe, Olabimpe C Badejogbin, Isaac O Ajadi, Mary B Ajadi

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Abstract

Purpose: Polycystic ovarian syndrome (PCOS) has been associated with cardiovascular risks and comorbid pathologies, particularly cardiorenal disorder. Short-chain fatty acids (SCFAs), especially butyrate, are essential fatty acids that regulate metabolic health and ameliorate granulosa inflammation in PCOS. However, the effect of butyrate on cardiorenal damage associated with PCOS is unknown. This study investigated the impact of SCFA and butyrate on cardiorenal abnormalities in PCOS rat model and the probable involvement of paraoxonase-1 (PON-1).

Methods: Eight-week-old female Wistar rats were allotted into three groups, n = 5, namely control (CTL), PCOS (LEZ), and LEZ + BUT. Induction of PCOS with letrozole (1 mg/kg) lasted for 21 days, while treatment with butyrate (200 mg/kg) commenced after the induction and lasted for 6 weeks uninterruptedly.

Results: PCOS rats showed hyperandrogenism, multiple ovarian cysts, disrupted metabolic indices (fasting insulin and homeostatic model of insulin resistance), and increased (p < 0.05) plasma troponin T, urea, and creatinine, as well as increased cardiac/renal stroma cell-derived factor-1/caspase-6, malondialdehyde/nuclear factor-kappaB, transforming growth factor-β1, and renal ϒ-glutamyl transferase, while a significant decrease (p < 0.05) in systemic nitric oxide/endothelial nitric oxide synthase and cardiac/renal hypoxia-inducible factor-1α and nuclear factor erythroid 2-related factor 2, which were accompanied with a decreased level of PON-1. These systemic and cardiorenal derangements were reversed by butyrate administration.

Conclusions: The results demonstrate the therapeutic benefits of SCFAs, butyrate, against cardiorenometabolic disorder in a model of PCOS. This beneficial effect is accompanied by an elevated level of PON-1. The present data possibly provides a preclinical relevance for the management of cardiorenal syndrome in PCOS.

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丁酸盐介导的副氧合酶-1调节可缓解多囊卵巢综合征大鼠模型中的心肾代谢异常。

目的：多囊卵巢综合征（PCOS）与心血管风险和合并病症，尤其是心肾功能紊乱有关。短链脂肪酸（SCFAs），尤其是丁酸盐，是调节多囊卵巢综合症患者代谢健康和改善颗粒炎症的必需脂肪酸。然而，丁酸盐对多囊卵巢综合症相关心肾损害的影响尚不清楚。本研究探讨了 SCFA 和丁酸盐对 PCOS 大鼠心肾功能异常的影响以及副氧合酶-1（PON-1）的可能参与：用来曲唑（1毫克/千克）诱导PCOS大鼠21天，丁酸盐（200毫克/千克）在诱导后开始治疗，连续6周：结果：多囊卵巢综合征大鼠表现出雄激素过多、多发性卵巢囊肿、代谢指标（空腹胰岛素和胰岛素抵抗稳态模型）紊乱以及胰岛素抵抗（p 结论）增加：研究结果表明，在多囊卵巢综合征模型中，SCFAs 和丁酸盐对心血管代谢紊乱有治疗作用。这种益处伴随着 PON-1 水平的升高。目前的数据可能为治疗多囊卵巢综合症的心肾综合征提供了临床前的相关性。

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来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.