Sympathoinhibition and vasodilation contribute to the acute hypotensive response of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, in hypertensive animals

Schlichte, Sarah L.; Pekas, Elizabeth J.; Bruett, Taylor; Kosmacek, Elizabeth A.; Hackfort, Bryan T.; Rasmussen, Jordan M.; Patel, Kaushik P.; Park, Song-Young; Oberley‐Deegan, Rebecca E.; Zimmerman, Matthew C.

doi:10.1016/j.arres.2021.100016

Cited by 3 publications

(2 citation statements)

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“…The likely mechanism for the association is through the antioxidant enzyme MnSOD, which scavenges reactive oxygen species, such as superoxide anions, that are associated with hypertension. 125 However, we did not observe associations with preeclampsia, which is contrary to the existing literature. Using data from two birth cohorts, Liu et al.…”

Section: Discussioncontrasting

confidence: 99%

Individual, Independent, and Joint Associations of Toxic Metals and Manganese on Hypertensive Disorders of Pregnancy: Results from the MIREC Canadian Pregnancy Cohort

Borghese

Fisher

Ashley‐Martin

et al. 2023

Environ Health Perspect

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Background: Toxic metals, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg), may be associated with a higher risk of gestational hypertension and preeclampsia, whereas manganese (Mn) is an essential metal that may be protective. Objectives: We estimated the individual, independent, and joint associations of Pb, Cd, As, Hg, and Mn on the risk of developing gestational hypertension and preeclampsia in a cohort of Canadian women. Methods: Metal concentrations were analyzed in first and third trimester maternal blood ( ). We measured blood pressure after 20 wk gestation to diagnose gestational hypertension, whereas proteinuria and other complications defined preeclampsia. We estimated individual and independent (adjusted for coexposure) relative risks (RRs) for each doubling of metal concentrations and examined interactions between toxic metals and Mn. We used quantile g-computation to estimate the joint effect of trimester-specific exposures. Results: Each doubling of third trimester Pb ( ; 95% CI: 1.06, 2.22) and first trimester blood As ( ; 95% CI: 1.01, 1.58) was independently associated with a higher risk of developing preeclampsia. First trimester blood As ( ; 95% CI: 1.40, 8.28) and Mn ( ; 95% CI: 0.42, 0.94) concentrations were associated with a higher and lower risk, respectively, of developing gestational hypertension. Mn modified the association with As such that the deleterious association with As was stronger at lower concentrations of Mn. First trimester urinary dimethylarsinic acid concentrations were not associated with gestational hypertension ( ; 95% CI: 0.60, 2.85) or preeclampsia ( ; 95% CI: 0.68, 1.24). We did not observe overall joint effects for blood metals. Discussion: Our results confirm that even low blood Pb concentrations are a risk factor for preeclampsia. Women with higher blood As concentrations combined with lower Mn in early pregnancy were more likely to develop gestational hypertension. These pregnancy complications impact maternal and neonatal health. Understanding the contribution of toxic metals and Mn is of public health importance. https://doi.org/10.1289/EHP10825

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Section: Discussioncontrasting

confidence: 99%

Individual, Independent, and Joint Associations of Toxic Metals and Manganese on Hypertensive Disorders of Pregnancy: Results from the MIREC Canadian Pregnancy Cohort

Borghese

Fisher

Ashley‐Martin

et al. 2023

Environ Health Perspect

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“…BMX-001 is currently in two Phase II studies—one in combination with radiation therapy and tamazolamide in glioblastoma and high-grade glioma and another in patients with multiple brain metastases (MBM) undergoing whole brain radiation therapy. In addition, the safety and tolerability of BMX-001 are currently being evaluated in two Phase I/II studies using a combination approach of BMX-001, standard radiation therapy (RT), and cisplatin in head and neck cancer patients to reduce radiation-induced mucositis and xerostomia, and in combination with 5-FU in anal squamous cell carcinoma (ASCC) (ClinicalTrials: NCT02655601 , NCT02990468 , NCT03386500 , NCT03608020 ) [ 212 ].…”

Section: Targeting Mitochondria As a Therapeutic Strategymentioning

confidence: 99%

Interplay between Mitochondrial Metabolism and Cellular Redox State Dictates Cancer Cell Survival

Foo

Hirpara

et al. 2021

Oxidative Medicine and Cellular Longevity

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Mitochondria are the main powerhouse of the cell, generating ATP through the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS), which drives myriad cellular processes. In addition to their role in maintaining bioenergetic homeostasis, changes in mitochondrial metabolism, permeability, and morphology are critical in cell fate decisions and determination. Notably, mitochondrial respiration coupled with the passage of electrons through the electron transport chain (ETC) set up a potential source of reactive oxygen species (ROS). While low to moderate increase in intracellular ROS serves as secondary messenger, an overwhelming increase as a result of either increased production and/or deficient antioxidant defenses is detrimental to biomolecules, cells, and tissues. Since ROS and mitochondria both regulate cell fate, attention has been drawn to their involvement in the various processes of carcinogenesis. To that end, the link between a prooxidant milieu and cell survival and proliferation as well as a switch to mitochondrial OXPHOS associated with recalcitrant cancers provide testimony for the remarkable metabolic plasticity as an important hallmark of cancers. In this review, the regulation of cell redox status by mitochondrial metabolism and its implications for cancer cell fate will be discussed followed by the significance of mitochondria-targeted therapies for cancer.

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Encapsulation of Manganese Porphyrin in Chondroitin Sulfate-A Microparticles for Long Term Reactive Oxygen Species Scavenging

et al. 2022

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Sympathoinhibition and vasodilation contribute to the acute hypotensive response of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, in hypertensive animals

Cited by 3 publications

References 50 publications

Individual, Independent, and Joint Associations of Toxic Metals and Manganese on Hypertensive Disorders of Pregnancy: Results from the MIREC Canadian Pregnancy Cohort

Individual, Independent, and Joint Associations of Toxic Metals and Manganese on Hypertensive Disorders of Pregnancy: Results from the MIREC Canadian Pregnancy Cohort

Interplay between Mitochondrial Metabolism and Cellular Redox State Dictates Cancer Cell Survival

Encapsulation of Manganese Porphyrin in Chondroitin Sulfate-A Microparticles for Long Term Reactive Oxygen Species Scavenging

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