Diacerein ameliorates letrozole-induced polycystic ovarian syndrome in rats

• Published in: Biomedicine & pharmacotherapy Vol. 149; p. 112870
• Main Authors: Ibrahim, Yasmine F., Alorabi, Mohammed, Abdelzaher, Walaa Yehia, Toni, Nisreen DM, Thabet, Khaled, Hegazy, AbdelRahman, Bahaa, Haitham Ahmed, Batiha, Gaber El-Saber, Welson, Nermeen N., Morsy, Mohamed A., Venugopala, Katharigatta N., Abdel-Aziz, Asmaa Mohamed
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2022; Elsevier
• Subjects: Animals; Anthraquinones - adverse effects; Diacerein; Disease Models, Animal; Female; Humans; IL-1β; Inflammatory response; Letrozole - adverse effects; Letrozole-induced polycystic ovarian syndrome; Metformin; Oxidative stress; Polycystic Ovary Syndrome - chemically induced; Polycystic Ovary Syndrome - drug therapy; Rats; Rats, Wistar; Letrozole-induced polycystic ovarian syndrome; Oxidative stress; Inflammatory response; Metformin; IL-1β; Diacerein
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.112870

Polycystic ovary syndrome (PCOS) is the most common gynaecological endocrine disease that causes anovulatory infertility. The current study aimed to explore the possible role of diacerein (DIA), an IL-1β inhibitor, in treating letrozole-induced PCOS in rats that exhibit the metabolic and endocrinal criteria of PCOS patients. PCOS was induced in female Wistar rats by the oral administration of letrozole (1 mg/kg, per orally, p.o.) for 21 days. Rats were then treated with DIA (25 mg/kg/day, p.o.), DIA (50 mg/kg/day, p.o.), or metformin (2 mg/100 g/day, p.o.) for 14 days after the PCOS induction. PCOS resulted in a significantly higher body weight, ovarian weight, ovarian size, and cysts, as well as an elevation in serum testosterone, LH, insulin, glycemia, and lipid profile levels. All of these effects were significantly reduced by the DIA administration. Additionally, DIA remarkably inhibited the letrozole-induced oxidative stress in the ovaries, muscles, and liver by reducing the upraised levels of malondialdehyde and total nitrite and increasing the suppressed levels of superoxide dismutase and catalase. DIA enhanced the protective proteins Keap-1, Nrf2, and OH-1 levels. Finally, DIA inhibited the elevated mRNA levels of NLRP3 and caspase-1, the up-regulated inflammatory cytokines IL-6, TNF-α, and the IL-1β/NFκB signaling pathway. Our results proved that DIA ameliorates letrozole-induced PCOS through its antioxidant and anti-inflammatory properties. [Display omitted] •Diacerein ameliorates letrozole-induced polycystic ovarian syndrome in rats.•Diacerein has significant antioxidant, and anti-inflammatory effects.•Diacerein up-regulates Keap-1/Nrf2/OH-1 signaling pathway.•Diacerein suppresses NLRP3/IL-1β /NFκB signaling pathway.