Targeting Aquaporin-5 by Phosphodiesterase 4 Inhibition Offers New Therapeutic Opportunities for Ovarian Ischemia Reperfusion Injury in Rats

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2024-07, Vol.31 (7), p.2021-2031
• Main Authors: Bozkurt, Ayse, Karakoy, Zeynep, Aydin, Pelin, Ozdemir, Bengul, Toktay, Erdem, Halici, Zekai, Cadirci, Elif
• Format: Article
• Language: English
• Subjects: Animals; Aquaporin 5 - metabolism; Cyclic AMP - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism; Embryology; Female; Infertility: Original; Infertility: Original Article; Interleukin-6 - metabolism; Medicine; Medicine & Public Health; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Obstetrics/Perinatology/Midwifery; Ovary - blood supply; Ovary - drug effects; Ovary - metabolism; Ovary - pathology; Phosphodiesterase 4 Inhibitors - pharmacology; Phosphodiesterase 4 Inhibitors - therapeutic use; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reproductive Medicine; Rolipram - pharmacology; Rolipram - therapeutic use; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1933-7191; 1933-7205; 1933-7205
• DOI: 10.1007/s43032-024-01496-w

This study aimed to examine the effect of Phosphodiesterase 4 (PDE4) inhibition on Aquaporin-5 (AQP5) and its potential cell signaling pathway in the ovarian ischemia reperfusion (OIR) model. Thirty adult female rats were divided into five groups: Group 1; Control: Sham operation, Group 2; OIR that 3 hour ischemia followed by 3 hour reperfusion, Group 3; OIR + Rolipram 1 mg/kg, Group 4; OIR + Rolipram 3 mg/kg, Group 5; OIR + Rolipram 5 mg/kg. Rolipram was administered intraperitoneally to the rats in groups 3-4 and 5 at determined doses 30 minutes before reperfusion. From ovary tissue; Tumor necrosis factor-a (TNF-α), Cyclic adenosine monophosphate (cAMP), Nuclear factor kappa (NF-κB), Interleukin-6 (IL-6), Phosphodiesterase 4D (PDE4D), Mitogen-activated protein kinase (MAPK) and AQP5 levels were measured by ELISA. We also measured the level of AQP5 in ovary tissue by real-time reverse-transcription polymerase chain reaction (RT-PCR). In the OIR groups; TNF-α, NF-κB, IL-6, MAPK inflammatory levels increased, and cAMP and AQP5 levels decreased, which improved with the administration of rolipram doses. Also histopathological results showed damaged ovarian tissue after OIR, while rolipram administration decrased tissue damage in a dose dependent manner. We propose that the protective effect of PDE4 inhibition in OIR may be regulated by AQP5 and its potential cell signaling pathway and may be a new target in OIR therapy. However, clinical studies are needed to appraise these data in humans.