Remifentanil Attenuates LPS-Induced Genital Tract Injury by Modulating Inflammation, Oxidative Stress, and Mitochondrial Gene Expression in a Rat Sepsis Model

Ozmen O., AŞCI H., Topsakal S., Taner R., ÖKTEM M., Ozcan K. N., ...More

Reproductive Sciences, vol.32, no.8, pp.2583-2594, 2025 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 32 Issue: 8
  • Publication Date: 2025
  • Doi Number: 10.1007/s43032-025-01930-7
  • Journal Name: Reproductive Sciences
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Food Science & Technology Abstracts, MEDLINE
  • Page Numbers: pp.2583-2594
  • Keywords: Apoptosis, Caspase, Genital Tract, Inflammation, LPS, NRF2, Oxidative Stress, Rat Model, Remifentanil
  • Kütahya Health Sciences University Affiliated: Yes

Abstract

Lipopolysaccharide (LPS), a key component of Gram-negative bacterial cell walls, triggers strong inflammatory responses that can severely impair reproductive organs. The female genital tract—including the ovaries, fallopian tubes, and uterus—is particularly vulnerable to LPS-induced inflammation, oxidative stress, and apoptosis. This study investigated the protective effects of remifentanil (REMI), an ultra-short-acting opioid with anti-inflammatory and antioxidant properties, against LPS-induced injury in female Wistar albino rats. Thirty-two rats were divided into four groups: LPS, LPS + REMI, REMI, and Control. LPS (5 mg/kg, i.p.) and REMI (0.04 mg/kg, i.v.) were administered, followed by histopathological, immunohistochemical (TNF-α, NF-κB, iNOS), and RT-qPCR analyses (Caspase-3, -9, -12, NRF2, HO-1) of the ovaries, uterus, and fallopian tubes. LPS exposure caused severe histological damage, increased inflammatory markers, and elevated caspase activity, particularly in the fallopian tubes and uterus. REMI treatment significantly reduced these pathological changes, restored NRF2 and HO-1 expression, and suppressed caspase activation. These findings indicate that REMI effectively protected against LPS-induced genital tract injury by modulating inflammation, reducing oxidative stress, and preventing apoptosis, highlighting its potential as a therapeutic agent for sepsis-related reproductive organ damage.