Document Type : Original Article
Authors
1
Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.
2
Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt.
3
Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
4
Department of Obstetrics and gynecology, Faculty of Medicine, Minia University, Minia, Egypt
5
Department of Obstetrics and gynecology, Faculty of Medicine, Minia University, Minia, Egypt.
Abstract
Introduction: Polycystic ovarian syndrome (PCOS) is the most common endocrinal pathology that
causes anovulatory infertility. This study explored the possible therapeutic effect of tocilizumab
(TCZ), an interleukin (IL)-6 receptor inhibitor in PCOS induced by letrozole in female Wistar rats,
which settled both clinical and metabolic criteria as in PCOS patients. Methods: Letrozole (1 mg/kg)
was administered per orally (p.o.) for a period of 21 days for the induction of PCOS. TCZ was then
followed in a dose of either (4 mg/kg, i.p.) or (8 mg/kg, i.p.), once weekly for 3 doses. Metformin (2
mg/100 g/day, p.o.) was utilized as a standard group using 0.1% w/v CMC as vehicle. Results: The
administration of TCZ significantly reduced the increase in body weight, ovarian diameter, and cysts,
as well as abnormalities in serum sex steroid, insulin, glucose levels, and lipid profile levels
demonstrated in PCOS group. Besides, TCZ significantly decreased the elevation in oxidative stress
parameters, and normalized the depletion in antioxidant activity reported in the PCOS rats. Moreover,
TCZ exhibited a significant reduction in the elevated serum levels of tumor necrosis factor (TNF)-
and IL-6. Finally, Letrozole induces a remarkable increase in ovarian angiogenic markers, vascular
endothelial growth factor (VEGF), angiopoietin (ANGPT), and platelet-derived growth factor
(PDGF), while TCZ was able to successfully reduce these markers to baseline levels. Conclusion:
TCZ showed beneficial effects in Letrozole induced PCOS in rats. Its effect was parallel to that of
metformin, the most widely used remedy in PCOS condition. Thus, its ability to block the IL-6
receptor, restore the ovarian function and exerts anti-androgenic, anti-metabolic, antioxidant, and antiangiogenic effects may offer an advantageous therapeutics for PCOS.
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