Febuxostat attenuates cyclophosphamide-induced ovarian toxicity; role of TLR4/NFκB/NLRP3 signaling pathway in female wistar albino rats.

BACKGROUND

Our goal was to assess if febuxostat (FEB) could prevent ovarian damage caused by cyclophosphamide (CP).

MATERIAL AND

METHODS

Four sets were created: control group, FEB group: received FEB 10 mg/kg orally for 14 days, CPgroup: a single ip dose of CP (200 mg/kg) at 8th day and CP+FEB group. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), malondialdehyde (MDA), total antioxidant capacity (TAC), interluken-6 (IL-6), tumor necrosis factor alpha (TNF-α), Nod-like receptor protein 3 (NLRP3) were estimated. Apoptotic Bcl-2-associated protein x (Bax) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl2) gene expression were measured. Histological alterations and immuno-expression of nuclear factor-kappa B (NF-κB) and toll like receptor4 (TLR4) were assessed.

RESULTS

FSH, LH, MDA, IL-6, TNF-α, NLRP3 levels, Bax and Bax/Bcl-2 ratio gene expression, NF-κB and TLR4 immuno-expression were all significantly elevated in the CP group. AMH, TAC levels and Bcl-2 gene expression have significantly decreased. Every metric indicated a notable improvement with FEB.

CONCLUSION

By controlling the TLR4/NF-Κb/NLRP3 signaling pathway, FEB has strong mitigating effects against oxidative stress, inflammatory processes, and apoptosis that result from CP-induced ovarian toxicity.