Ameliorating effect of tocilizumab in letrozole induced polycystic ovarian syndrome in rats via improving insulin resistance and down-regulation of VEGF/ANGPT/PDGF | ||||
| Minia Journal of Medical Research | ||||
| Volume 31, Issue 1, January 2020, Page 336-353 PDF (749.67 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/mjmr.2022.221583 | ||||
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| Authors | ||||
| Yasmine F. Ibrahim1; Nisreen D. M. Toni2; Khaled Thabet3; AbdelRahman Hegazy4; Haitham A. Bahaa5 | ||||
| 1Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt. | ||||
| 2Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt. | ||||
| 3Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt. | ||||
| 4Department of Obstetrics and gynecology, Faculty of Medicine, Minia University, Minia, Egypt | ||||
| 5Department 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. | ||||
| Keywords | ||||
| Tocilizumab; Metformin; Polycystic ovarian syndrome; IL-6; Angiogenesis; Insulin resistance | ||||
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