Galaxamide Ameliorates Cisplatin-induced Uterine Injury via Anti‑inflammatory and Antiapoptotic Mechanisms in Mice

Cisplatin treatment can cause ovarian dysfunction, but its impact on uterine function remains poorly defined. Although galaxamide increases the antitumor efficacy of cisplatin and protects ovarian function, its effects on uterine health are unknown. HeLa tumor‑bearing female mice received CIS alone or in combination with galaxamide. We assessed uterine morphology, systemic inflammation, endometrial epithelial cell apoptosis, endometrial receptivity factor expression, macrophage polarization, and NF-κB signaling. Cisplatin induced epithelial thinning and glandular disorganization; promoted apoptosis; decreased the expression of receptivity markers and desmosome and tight junction integrity; and elevated the serum levels of IL-6, IL-18, and TNF-α. Moreover, M1 macrophage infiltration and NF-κB pathway activation were observed. Cotreatment with galaxamide reduced cytokine levels, preserved uterine architecture, normalized apoptotic gene expression, restored receptivity marker expression, maintained desmosome/tight junction integrity, promote M2 macrophage polarization, and inhibited NF‑κB activation. In this study, cisplatin-induced uterine injury in tumor-bearing model mice was characterized. Galaxamide was demonstrated to attenuate this damage through antiapoptotic and anti-inflammatory actions mediated by inhibition of the NF-κB signaling pathway, suggesting its potential as a protective adjuvant to mitigate uterine toxicity during CIS‑based chemotherapy.