Vonoprazan attenuates cyclophosphamide-induced ovarian injury in rats via modulation of TLR4/NF-κB and AMPK/SIRT1/Nrf2/HO-1 signaling.

Authors

Al Shaimaa Mahmoud Kotb, Ehab E Sharata, Reham H Mohyeldin, Mina Ezzat Attya, Mahmoud Abdelnaser, Hadeer M Farhan, Magdi E A Zaki, Sobhi M Gomha, Yassmen Mohamed Montaser A Khalifa

Published in

Tissue & cell. Volume 104. Issue Pt 3. Pages 104080. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

Cyclophosphamide (CPA) is a widely used alkylating agent that causes premature ovarian insufficiency (POI), a major reproductive risk for young female cancer survivors. This study examined whether vonoprazan (VON), a potassium-competitive acid blocker with reported cytoprotective activity in non-gastric tissues, protects against CPA-induced ovarian injury in female Wistar albino rats, and characterized the signaling changes that accompany this protection. Rats (n = 10 per group) received saline, VON (20 mg/kg/day, p.o.), CPA (200 mg/kg i.p. on day 1 followed by 8 mg/kg/day for 14 days), or CPA with concurrent VON. CPA reduced body and ovarian weights, disrupted estrous cyclicity, lowered serum estradiol and AMH while raising FSH, increased ovarian lipid peroxidation and pro-inflammatory cytokines, depleted antioxidant enzymes, elevated cleaved caspase-3, upregulated TLR4 and NF-κB p65, and reduced p-AMPK, SIRT1, Nrf2 and HO-1. Histological examination confirmed widespread follicular degeneration and loss of follicles across all developmental classes. Concurrent VON significantly attenuated each of these changes and preserved ovarian architecture and follicular reserve. These findings show that VON, given alongside CPA, protects the rat ovary against alkylating-agent injury, and that this protection is associated with suppression of TLR4/NF-κB signaling and restoration of the p-AMPK/SIRT1/Nrf2/HO-1 axis. Because pathway involvement was inferred from changes in protein abundance rather than tested by pharmacological or genetic interruption, these associations require causal confirmation, and the relevance of VON to clinical fertility preservation remains to be established.

PMID:
42913187
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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