Ketogenic diet restores hormonal, apoptotic/proliferative balance and enhances the effect of metformin on a letrozole-induced polycystic ovary model in rats.

Autor: Ahmed AF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt. Electronic address: Shaimaa_faissal@minia.edu.eg., Sharkawi SS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt., AbdelHameed SS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt., Bayoumi AM; Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt., Moussa RS; Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt., Alhakamy NA; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Al Sadoun H; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Mansouri RA; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia., El-Moselhy MA; Clinical Pharmacy and Pharmacology Department, Ibn Sina National College for Medical Studies, Jeddah 21589, Saudi Arabia., El-Daly M; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt., Anter AF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Jan 15; Vol. 313, pp. 121285. Date of Electronic Publication: 2022 Dec 13.
DOI: 10.1016/j.lfs.2022.121285
Abstrakt: Objective: Polycystic ovaries (PCO) is a hormonal disorder that is a leading cause of infertility. The formation of multiple persistent cysts and hormonal imbalance are hallmarks of PCO. Recent clinical studies reported a beneficial effect of the ketogenic diet (KD; high-fat, low-carbohydrate) on PCO. The aim of this study was to investigate the effect of the KD alone and in combination with metformin on letrozole-induced PCO in female rats.
Methods: Female rats were grouped into control and PCO (letrozole; 1 mg/kg for 21 days). The PCO group was subdivided into PCO (non-treated), PCO-metformin (300 mg/kg), PCO rats fed with KD only, and PCO rats treated with metformin and fed with KD. All groups continued to receive letrozole during the 21-day treatment period. At the end of the experiment, serum and ovaries were collected for further analysis.
Results: The untreated-PCO rats showed increased testosterone, LH/FSH ratio, and ovary weights. Disturbed apoptosis and proliferation balance were evident as a low caspase-3 activation and proliferating cell nuclear antigen expression and increased TGF-β expression. The KD improved the letrozole-induced effects, which was comparable to the effect of metformin. Combining the KD with metformin treatment additively enhanced the metformin effect.
Conclusion: Our results indicate that the KD has a protective role against PCO in rats, especially when combined with metformin. This study reveals a potential therapeutic role of the KD in PCO, which could prompt valuable future clinical applications.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE