2-Methoxyestradiol ameliorates metabolic syndrome-induced hypertension and catechol-O-methyltransferase inhibited expression and activity in rats

Azhar, Abdullah Zoheb; Zaher, Zaher F.; Ashour, Osama M.; Abdel-Naim, Ashraf B.

doi:10.1016/j.ejphar.2020.173278

Cited by 9 publications

(2 citation statements)

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“…It possesses pleotropic pharmacological actions. These include anticancer [ 20 ], antihypertensive [ 21 , 22 ], vascular-protective [ 23 ], and neuroprotective [ 24 ] activities. 2-Methoxyestradiol was shown to prevent kidney damage and improves survival in septic mice via inhibiting the production of cytokines and nitric oxide [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis

Al-Rabia

Alfaleh²,

Asfour³

et al. 2022

Antioxidants

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The immunosuppressant cyclosporine A (CSA) has been linked to serious renal toxic effects. Although 2-methoxyestradiol (2ME) possesses a wide range of pharmacological abilities, it suffers poor bioavailability after oral administration. The purpose of this study was to evaluate the potential of 2ME loaded D-ɑ-tocopheryl polyethylene glycol succinate (TPGS) micelles to prevent CSA-induced nephrotoxicity in rats. A 2ME-TPGS was prepared and showed particle size of 44.3 ± 3.5 nm with good entrapment efficiency and spherical structures. Male Wistar rats were divided into 5 groups, namely: Control, Vehicle, CSA, CSA + 2ME-Raw, and CSA + 2ME-Nano. CSA was injected daily at a SC dose of 20 mg/kg. Both 2ME-Raw and 2ME-Nano were given daily at oral doses of 5 mg/kg. Treatments continued for three successive weeks. 2ME-TPGS exerted significant protective effects against CSA nephrotoxicity. This was evidenced in ameliorating deterioration of renal functions, attenuation of pathological changes in kidney tissues, exerting significant anti-fibrotic, antioxidant, and anti-inflammatory effects together with significant anti-apoptotic effects. Western blot analyses showed both 2ME-Raw and 2ME-Nano significantly inhibited protein expression of TGF-β1 and phospho-ERK (p-ERK). It was observed that 2ME-TPGS, in almost all experiments, exerted superior protective effects as compared with 2ME-Raw. In conclusion, 2ME loaded in a TPGS nanocarrier possesses significant protective activities against CSA-induced kidney injury in rats. This is attributable to 2ME anti-fibrotic, antioxidant, anti-inflammatory, and anti-apoptotic activities which are mediated at least partly by inhibition of TGF-β1/p-ERK axis.

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Section: Introductionmentioning

confidence: 99%

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis

Al-Rabia

Alfaleh²,

Asfour³

et al. 2022

Antioxidants

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“…9 In addition, treatment with 2-ME protects against development of hypertension in Ang II–induced hypertension and in metabolic syndrome–associated hypertension. 10,11 In addition, growing evidence indicates that COMT-deficient mice have a preeclampsia-like phenotype, with hypertension developing on day 17 of pregnancy. 12 Clinical studies also suggest that COMT is downregulated in patients with preeclampsia, since levels of COMT and 2-ME are significantly lower in placentas from preeclamptic patients compared with normotensive counterparts.…”

mentioning

confidence: 99%

Mg ²⁺ Channels as the Link Between Mg ²⁺ Deficiency and COMT Downregulation in Salt-Sensitive Hypertension

Touyz

2021

Hypertension

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Mechanisms of Dopamine Oxidation and Parkinson’s Disease

Segura‐Aguilar

Paris

2022

Handbook of Neurotoxicity

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2-Methoxyestradiol ameliorates metabolic syndrome-induced hypertension and catechol-O-methyltransferase inhibited expression and activity in rats

Cited by 9 publications

References 48 publications

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis

Mg ²⁺ Channels as the Link Between Mg ²⁺ Deficiency and COMT Downregulation in Salt-Sensitive Hypertension

Mechanisms of Dopamine Oxidation and Parkinson’s Disease

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2-Methoxyestradiol ameliorates metabolic syndrome-induced hypertension and catechol-O-methyltransferase inhibited expression and activity in rats

Cited by 9 publications

References 48 publications

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis

Mg 2+ Channels as the Link Between Mg 2+ Deficiency and COMT Downregulation in Salt-Sensitive Hypertension

Mechanisms of Dopamine Oxidation and Parkinson’s Disease

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Mg ²⁺ Channels as the Link Between Mg ²⁺ Deficiency and COMT Downregulation in Salt-Sensitive Hypertension