2. Academic Validation
  3. Synergistic action of carvedilol and clomiphene in mitigating the behavioral phenotypes of letrozole-model of PCOS rats by modulating the NRF2/NFKB pathway

Synergistic action of carvedilol and clomiphene in mitigating the behavioral phenotypes of letrozole-model of PCOS rats by modulating the NRF2/NFKB pathway

  • Life Sci. 2023 Jul 1:324:121737. doi: 10.1016/j.lfs.2023.121737.
Olabode Oluwadare Akintoye 1,  Ayodeji Johnson Ajibare 2,  Isaac Adeola Oriyomi 3,  Babatunde Ajayi Olofinbiyi 4,  Grace Oyiza Yusuf 3,  Damilola Christanah Afuye 3,  Temitope Kabirat Babalola 2,  Oluwadamilola Esther Faturoti 3,  Seun Oludipe 3,  Victor Bamidele Owoyele 5
Affiliations

Affiliations

  • 1 Physiology Department, College of Medicine, Ekiti State University, Ado Ekiti, Nigeria. Electronic address: [email protected].
  • 2 Lead city University, Ibadan, Nigeria.
  • 3 Physiology Department, College of Medicine, Ekiti State University, Ado Ekiti, Nigeria.
  • 4 Department of Obstetrics and Gynaecology, College of Medicine, Ekiti State University, Ado-Ekiti, Ekiti State, Nigeria.
  • 5 Physiology Department, Faculty of Basic Medical Sciences, College of Health Science, University of Ilorin, Nigeria.
PMID: 37127183 DOI: 10.1016/j.lfs.2023.121737
Abstract

Introduction: Psychiatric and cognitive impairment has been observed in premenopausal women with a hormonal disorder called polycystic ovary syndrome (PCOS). This study aimed to explore the possibility of combining pharmacological agents: Carvedilol and Clomiphene citrate, with antiestrogenic, antioxidant and anti-inflammatory properties in letrozole-induced PCOS rats.

Methods: PCOS was induced in rats by the administration of letrozole (1 mg/kg) daily for 21 days. They were subsequently divided into four groups, each receiving either the vehicle or Clomiphene citrate (1 mg/kg) or Carvedilol or a combination of Clomiphene citrate and Carvedilol, respectively from days 22-36. Neurobehavioral studies were conducted on day 35 (Elevated plus maze and Y maze) and day 36 (Novel object recognition). The serum levels of the antioxidants Superoxide dismutase, Catalase, Interleukin 1B (IL-1B), and the gene expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), Nuclear Factor k-Beta (NFKB), and acetylcholine esterase in the frontal brain homogenate was determined.

Result: Both Carvedilol and the combination therapy reversed the anxiety-like behavior, while Clomiphene citrate and the combination therapy ameliorated the spatial and non-spatial memory impairment observed in PCOS rats. Carvedilol, Clomiphene citrate, and the combination therapy increased the serum concentration of SOD and Catalase and decreased the serum concentration of IL-1B. The combination therapy up-regulated the NRF-2, NFKB, and acetylcholine esterase gene expression.

Conclusion: Study showed that the combination of carvedilol and clomiphene citrate has anxiolytic potential and improved cognitive functions in PCOS rats. This might have been achieved by carvedilol and clomiphene citrate's ability to modulate the cholinergic system and the Nrf2 pathway while downregulating the NFκB signaling pathway.

Keywords

Carvedilol; Clomiphene; Cognition; Neurobehaviour; PCOS.

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