MZe786, a hydrogen sulfide-releasing aspirin prevents preeclampsia in heme oxygenase-1 haplodeficient pregnancy under high soluble flt-1 environment

Rezai, Homira; Ahmad, Shakil; Alzahrani, Faisal; Sanchez-Aranguren, Lissette; Dias, Irundika H.K.; Agrawal, Swati; Sparatore, Anna; Wang, Keqing; Ahmed, Asif

doi:10.1016/j.redox.2020.101768

Cited by 15 publications

(25 citation statements)

References 59 publications

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“…MZe786 has been shown to effectively reverse pathological symptoms in a rat model of metabolic syndrome [ 48 ]. The study compared the effect of MZe786 with its parent compound aspirin and confirmed the clear beneficial effect of MZe786 over aspirin [ 21 , 48 ]. Since the clear beneficial role of MZe786 over aspirin was already established, we chose not to include an aspirin-only group to minimise animal usage, as our objective was to see if MZe786 reduced sFlt-1 levels.…”

Section: Discussionmentioning

confidence: 88%

“…In conclusion, the development of this refined surgically induced model of preeclampsia that captures major preeclampsia features including up-regulation of sFlt-1 and down-regulation of protective enzymes offers a unique opportunity to test novel therapeutics for the prevention of preeclampsia. MZe786 significantly limited the development of preeclampsia in the mRUPP model by suppressing sFlt-1 and nitrosative stress as well as improving antioxidant genes [ 21 ] and cellular mitochondrial function [ 64 , 65 ]. This compound warrants urgent investigation in clinical settings.…”

Section: Discussionmentioning

confidence: 99%

“…The H 2 S-releasing molecule, MZe786 (2-acetyloxybenzoic acid 4-(3-thioxo-3 H -1,2-dithiol-5-yl)phenyl ester) with a defined pharmacological profile, was used as previously described [ [19] , [20] , [21] ].…”

Section: Methodsmentioning

confidence: 99%

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Hydrogen sulfide releasing molecule MZe786 inhibits soluble Flt-1 and prevents preeclampsia in a refined RUPP mouse model

Saif

Ahmad

Rezai³

et al. 2021

Redox Biology

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Hydrogen sulfide releasing molecule MZe786 inhibits soluble Flt-1 and prevents preeclampsia in a refined RUPP mouse model

Saif

Ahmad

Rezai³

et al. 2021

Redox Biology

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“…MZe786 reduced preeclampsia-stimulating antioxidant genes and then reduced hypertension and renal damage. MZe786 was also better for fetal outcomes in comparison with aspirin alone and was shown to be a good therapeutic agent in preventing preeclampsia [ 178 ].…”

Section: H 2 S Donors and Diseasesmentioning

confidence: 99%

H2S Donors and Their Use in Medicinal Chemistry

Magli¹,

Perissutti²,

Santagada³

et al. 2021

Biomolecules

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Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their -biological applications.

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“…Although inflammation has been implicated as a cause of pre-eclampsia (Redman et al, 1999), increasing evidence points to inflammation acting as an amplifier, rather than a causal factor (Ahmed et al, 2017;Ahmed & Ramma, 2015). Defects in two protective enzymes, haem oxygenase-1 (Cudmore et al, 2007) and cystathionine γ-lyase (Wang et al, 2013), lead to increases in sFlt-1 in the mother's circulation and appear to cause pre-eclampsia (Rezai et al, 2020;Saif et al, 2021). Chronic hypertension is a major risk factor for pre-eclampsia.…”

Section: Clinical Manifestations Of Covid-19 In Pregnant Women and Th...mentioning

confidence: 99%

The impact of COVID‐19 on pregnancy and therapeutic drug development

Abbas-Hanif

Rezai

Ahmed

et al. 2021

British J Pharmacology

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Emerging data shows pregnant women with COVID‐19 are at significantly higher risk of severe outcomes compared to non‐pregnant women of similar age. This review discusses the invaluable insight revealed from vaccine clinical trials in women who were vaccinated and inadvertently became pregnant during the trial period. It further explores a number of clinical avenues in their management and proposes a drug development strategy in‐line with clinical trials for vaccines and drug treatments for the drug development community. Little is known of the long‐term effects of COVID‐19 on the mother and the baby. Our hypothesis that COVID‐19 predisposes pregnant women to preeclampsia or hypertensive disorders during pregnancy is supported by a clinical study and this may also adversely impact a woman’s cardiovascular disease risk later in life. It may also increase the risk of preeclampsia in their subsequent pregnancy. This is an ever‐evolving landscape and early knowledge for healthcare providers and drug innovators is offered to ensure benefits outweigh the risks. COVID‐19 mRNA vaccines appear to generate robust humoral immunity in pregnant and lactating women. This novel approach to vaccination also offers new ways to therapeutically tackle disorders of many unmet medical needs.

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MZe786, a hydrogen sulfide-releasing aspirin prevents preeclampsia in heme oxygenase-1 haplodeficient pregnancy under high soluble flt-1 environment

Cited by 15 publications

References 59 publications

Hydrogen sulfide releasing molecule MZe786 inhibits soluble Flt-1 and prevents preeclampsia in a refined RUPP mouse model

Hydrogen sulfide releasing molecule MZe786 inhibits soluble Flt-1 and prevents preeclampsia in a refined RUPP mouse model

H2S Donors and Their Use in Medicinal Chemistry

The impact of COVID‐19 on pregnancy and therapeutic drug development

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