Sildenafil ameliorates leptin resistance and normalizes lipid handling in the hypothalamic and adipose tissues of testosterone-exposed pregnant rats

Areola, Emmanuel Damilare; Sabinari, Isaiah Woru; Usman, Taofeek; Abayomi, Faith Ifeoluwa; Onyezia, Onyeka; Onaolapo, Bisola; Adetokunbo, Phebe Oluwaseun; Adebanjo, O.O.; Oladipupo, Funmilayo Rebecca; Olatunji, Lawrence Aderemi

doi:10.1016/j.heliyon.2021.e07574

Cited by 1 publication

(2 citation statements)

References 37 publications

(36 reference statements)

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“…Cells adapts to oxidative stress by increasing the expression of Nrf2 in order to promote transcription of antioxidant genes. The severe oxidative/inflammatory stress during lipotoxicity impairs antioxidant function by decreasing Nrf2 level [ 16 ]. The observed decrease in ovarian GSH and GPx contents in this study is further corroborated by a significant reduction in Nrf2 level in PCOS rats.…”

Section: Discussionmentioning

confidence: 99%

“…The Nuclear Factor (Erythroid-Derived 2)–Like 2 (Nrf2) is a transcription factor and master regulator of antioxidant genes through interaction with nuclear antioxidant response element (ARE) leading to the expression of key antioxidants necessary for cytoprotection against reactive oxygen species (ROS) [ 15 ]. Polycystic ovary syndrome-related oxidative imbalance involves a down regulated Nrf2 which permits oxidative stress, and inflammatory response [ 16 ]. Glutathione (GSH) is an important thiol-based tripeptide involved in detoxification of free radicals and superoxides [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Short chain fatty acid, acetate restores ovarian function in experimentally induced PCOS rat model

et al. 2022

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Background Polycystic ovarian syndrome (PCOS) is pathogenically characterized with hyperandrogenism and metabolic alterations, which often result in ovarian changes and infertility in women of reproductive age. Epigenetic changes have been linked to the development of PCOS. However, the involvement of epigenetic regulator, histone deacetylase (HDAC) in PCOS-driven ovarian dysfunction is not clear. Howbeit, the present study hypothesized that acetate, an HDAC inhibitor (HDACi) would protect against ovarian dysfunction in experimentally induced PCOS. Materials and methods Female Wistar rats weighing 120–150 g were randomly divided into four groups (n = 6). The groups received vehicle, sodium acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole with acetate by oral gavage respectively. The administrations were done daily for 21 days. Results The rat model of PCOS had increased body weight and ovarian weight, 1-hr postload glucose and plasma insulin, testosterone and LH/FSH ratio as well as reduced insulin sensitivity and plasma 17-β estradiol and sex hormone binding globulin. This model of PCOS in addition showed a significant increase in plasma and ovarian triglyceride, total cholesterol, TNF-α and HDAC, and ovarian malondialdehyde as well as a significant reduction in ovarian glutathione peroxidase/reduced glutathione and NrF2 with the histology of ovarian tissues showing disrupted morphology with significant increase in the number of degenerated follicles compared with control group. These alterations were however attenuated when treated with HDACi, acetate. Conclusion Altogether, the present results suggest that acetate protects ovarian function with evidence of normal growing follicles and enhanced circulating 17-β estradiol by inhibition of HDAC.

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Section: Discussionmentioning

confidence: 99%