Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt.
Life Sci. 2022 May 1;296:120441. doi: 10.1016/j.lfs.2022.120441. Epub 2022 Feb 28.
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.
研究 17β 雌二醇（E2）及其内源性非激素代谢物 2-甲氧基雌二醇（2ME）对去卵巢（OVX）大鼠肾缺血再灌注（RIR）诱导的肾损伤的影响，以及儿茶酚-O-甲基转移酶（COMT）在其作用中的作用。
将 80 只雌性大鼠分为 8 组。对照组、假手术组、OVX 组、OVX 和 RIR 组、OVX+RIR+E2 组、OVX+RIR+2ME 组、OVX+RIR+E2+恩他卡朋组和 OVX+RIR+2ME+恩他卡朋组。RIR 后 24 小时，检测血清中肌酐（Cr）和血尿素氮（BUN）的含量，同时评估肾组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽（GSH）、髓过氧化物酶（MPO）、COMT、缺氧诱导因子-1α（HIF-1α）和酪氨酸羟化酶（TH）的表达。
与假手术组相比，OVX 和 RIR 组血清 Cr、BUN、MPO 以及 HIF-1α 和 TH 表达明显升高，COMT 表达降低，SOD 和 CAT 活性及 GSH 含量降低。E2 和 2ME 治疗可显著改善 OVX 和 RIR 大鼠的所有参数。另一方面，恩他卡朋显著降低了 E2 的作用，而对 2ME 治疗无影响。
E2 可改善 RIR 诱导的肾损伤，这种作用至少部分是通过其 COMT 介导的转化为 2ME 介导的。因此，2ME 由于其多效性的药理作用，可以作为 RIR 损伤的安全有效的治疗方法。
