Administration of hemin ameliorates ovarian ischemia reperfusion injury via modulation of heme oxygenase-1 and p-JNK/p-NF-κBp65/iNOS signaling pathway

• Published in: Life sciences (1973) 2022-05, Vol.296, p.120431, Article 120431
• Main Authors: Ali, Fatma F., Mokhemer, Sahar A., Elroby Ali, Doaa M.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis; Caspase 3 - metabolism; Caspase-3; Damage; Female; Gene Expression Regulation - drug effects; Glutathione; Heme; Heme oxygenase (decyclizing); Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase (Decyclizing) - metabolism; Hemin; Hemin - pharmacology; HO-1; IL-1β; Inflammation; Injury prevention; iNOS; Interleukin 1; Interleukin-1beta - blood; Ischemia; Janus kinase; Kinases; Malondialdehyde; MAP Kinase Kinase 4 - metabolism; NF-κB protein; Nitric oxide; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Ovarian ischemia reperfusion; Ovaries; Ovary - blood supply; Ovary - drug effects; Ovary - metabolism; Ovary - pathology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Oxygenase; P-JNK; P-NF-κB p65; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; Reproductive status; Serum levels; Signal transduction; Signal Transduction - drug effects; Superoxide dismutase; Transcription Factor RelA - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120431

Ovarian torsion is the fifth common gynecological emergency that can affect females of all ages particularly during reproductive age and its management by detorsion leads to ovarian ischemia reperfusion (IR) injury. Therefore, prophylactic measures are required to protect the ovarian function after detorsion. So that, our study aimed to assess the effect and underlying mechanisms of heme oxygenase-1 (HO-1) inducer; hemin against ovarian damage induced by IR injury in rats. Female rats were divided into: sham group, hemin group, ovarian IR (OIR) groups with and without hemin treatment. Serum levels of reduced glutathione (GSH) and interleukin 1 β (IL-1β) were measured in addition to ovarian levels of malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD). Ovarian phospho-Janus kinase (p-JNK) levels and gene expressions of HO-1 and inducible nitric oxide synthase (iNOS) were determined. Moreover, histopathological changes and expressions of phospho-nuclear factor kappa B p65 (p-NF-κB p65) and cleaved caspase-3 were done. Treatment of OIR rats with hemin led to significant attenuation of ovarian damage through histological examination which was associated with significant increase in ovarian expression of HO-1, ovarian SOD and serum GSH levels with significant decrease in ovarian p-JNK levels, expressions of p-NF-κB p65, iNOS and cleaved caspase-3 in addition to serum IL-1β levels. The protective effect of hemin can be attributed to the increased expression of HO-1 which showed antioxidant, anti-inflammatory and anti-apoptotic effects. Therefore, hemin can be administered to prevent ovarian IR injury which occurs after detorsion.