The potential protective effects of estradiol and 2-methoxyestradiol in ischemia reperfusion-induced kidney injury in ovariectomized female rats
Autor: | Eslam Hassan, Shady Allam, Ahmed M. Mansour, Aya Shaheen, Salama A. Salama |
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Rok vydání: | 2021 |
Předmět: |
Estradiol
Ovariectomy Body Weight Catechols General Medicine Catechol O-Methyltransferase Hypoxia-Inducible Factor 1 alpha Subunit Kidney Protective Agents General Biochemistry Genetics and Molecular Biology 2-Methoxyestradiol Blood Urea Nitrogen Enzymes Rats Sprague-Dawley Reperfusion Injury Nitriles Animals Female General Pharmacology Toxicology and Pharmaceutics |
Zdroj: | Life sciences. 296 |
ISSN: | 1879-0631 |
Popis: | 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. |
Databáze: | OpenAIRE |
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