The potential protective effects of estradiol and 2-methoxyestradiol in ischemia reperfusion-induced kidney injury in ovariectomized female rats

• Published in: Life sciences (1973) Vol. 296; p. 120441
• Main Authors: Hassan, Eslam, Allam, Shady, Mansour, Ahmed M., Shaheen, Aya, Salama, Salama A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2022; Elsevier BV
• Subjects: 17β-Estradiol; 2-Methoxyestradiol; 2-Methoxyestradiol - metabolism; 2-Methoxyestradiol - pharmacology; Animals; Blood Urea Nitrogen; Body Weight - drug effects; Catalase; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - metabolism; Catechols - pharmacology; Creatinine; Entacapone; Enzymes - metabolism; Estradiol; Estradiol - pharmacokinetics; Estradiol - pharmacology; Female; Glutathione; Hydroxylase; Hypoxia; Hypoxia inducible factor-1α; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Injuries; Ischemia; Kidney - blood supply; Kidney - drug effects; Kidney - pathology; Kidneys; Malondialdehyde; Metabolites; Methyltransferase; Nitriles - pharmacology; Ovariectomy; Peroxidase; Protective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Renal ischemia/reperfusion injury; Reperfusion; Reperfusion Injury - prevention & control; Rodents; Sex hormones; Superoxide dismutase; Tyrosine; Tyrosine 3-monooxygenase; Tyrosine hydroxylase; Urea; 2-Methoxyestradiol; Catechol-O-methyltransferase; Hypoxia inducible factor-1α; Renal ischemia/reperfusion injury; Entacapone; Tyrosine hydroxylase; Estradiol
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120441

Investigating the impact of 17β estradiol (E2) and its endogenous non-hormonal metabolite 2-methoxyestradiol (2ME) on renal ischemia-reperfusion (RIR) induced kidney injury in ovariectomized (OVX) rats and the role of catechol-O-methyltransferase (COMT) in their effects. Eighty female rats were allocated into eight groups. Control group, Sham group, OVX group, OVX and RIR group, OVX + RIR + E2 group, OVX + RIR + 2ME group, OVX + RIR + E2 + Entacapone group and OVX + RIR + 2ME + Entacapone group, respectively. Twenty-four hours post RIR, creatinine (Cr) and blood urea nitrogen (BUN) were determined in serum, while malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), Glutathione (GSH), myeloperoxidase (MPO), as well as the expressions of COMT, hypoxia inducible factor-1α (HIF-1α) and tyrosine hydroxylase (TH) were assessed in the kidney tissues. Serum Cr, BUN, MPO, as well as HIF-1α and TH expressions were significantly higher with concomitant decrease in COMT expression, SOD and CAT activities and GSH content observed in OVX and RIR group compared to sham group. E2 and 2ME treatment significantly ameliorated all parameters measured in OVX and RIR rats. On the other hand, Entacapone significantly decreased the effect of E2, with no effect on 2ME treatment. E2 ameliorates RIR-induced kidney injury and this effect is mediated, at least in part, via its COMT-mediated conversion to 2ME. Thus, 2ME by the virtue of its pleiotropic pharmacological effects can be used as a safe and effective treatment of RIR injury.