The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: A Systematic Review

Estarreja, João; Caldeira, Gonçalo; Silva, Inês; Mendes, Priscila; Mateus, Vanessa

doi:10.3390/biomedicines12040898

Cited by 2 publications

(1 citation statement)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both drugs are approved for treatments in humans, but only sildenafil has been used in neonates for cardiopulmonary problems, such as pulmonary hypertension and broncopulmonary dysplasia ( Dillon et al, 2023 ). Sildenafil was proposed as a potent vasodilator agent ( Kelly et al, 2017 ), while Hemin as an antiremodeling and antioxidant ( Estarreja et al, 2024 ) In this context, there is strong evidence that suggests a potentially beneficial outcome of using these two drugs in treatments to reverse the adverse effects of HAHH exposure. However, to the best of our knowledge, no studies have addressed the effects of hemin and sildenafil on neonatal aortas exposed to chronic hypoxia during the perinatal period.…”

Section: Introductionmentioning

confidence: 99%

Biomechanical effects of hemin and sildenafil treatments on the aortic wall of chronic-hypoxic lambs

Navarrete,

Inostroza,

Utrera

et al. 2024

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Introduction: Gestation under chronic hypoxia causes pulmonary hypertension, cardiovascular remodeling, and increased aortic stiffness in the offspring. To mitigate the neonatal cardiovascular risk, pharmacological treatments (such as hemin and sildenafil) have been proposed to improve pulmonary vasodilation. However, little is known about the effects of these treatments on the aorta. Therefore, we studied the effect of hemin and sildenafil treatments in the aorta of lambs gestated and raised at highlands, thereby subjected to chronic hypoxia.Methods: Several biomechanical tests were conducted in the descending thoracic aorta (DTA) and the distal abdominal aorta (DAA), assessing 3 groups of study of hypoxic animals: non-treated (Control) and treated either with hemin or sildenafil. Based on them, the stiffness level has been quantified in both zones, along with the physiological strain in the unloaded aortic duct. Furthermore, a morphological study by histology was conducted in the DTA.Results: Biomechanical results indicate that treatments trigger an increment of axial pre-stress and circumferential residual stress levels in DTA and DAA of lambs exposed to high-altitude chronic hypoxia, which reveals a vasodilatation improvement along with an anti-hypertensive response under this characteristic environmental condition. In addition, histological findings do not reveal significant differences in either structure or microstructural content.Discussion: The biomechanics approach emerges as a valuable study perspective, providing insights to explain the physiological mechanisms of vascular function. According to established results, alterations in the function of the aortic wall may not necessarily be explained by morphostructural changes, but rather by the characteristic mechanical state of the microstructural components that are part of the studied tissue. In this sense, the reported biomechanical changes are beneficial in mitigating the adverse effects of hypobaric hypoxia exposure during gestation and early postnatal life.

show abstract

Section: Introductionmentioning

confidence: 99%

Biomechanical effects of hemin and sildenafil treatments on the aortic wall of chronic-hypoxic lambs

Navarrete,

Inostroza,

Utrera

et al. 2024

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

Mitophagy modulation rescues single large-scale mitochondrial DNA deletion (SLSMD) disease symptoms in theC. elegans uaDf5animal model

Mendel,

Matsuno,

et al. 2024

Preprint

View full text Add to dashboard Cite

Single large scale mitochondrial DNA (mtDNA) deletions (SLSMD) underlie a range of sporadic or maternally inherited primary mitochondrial diseases having significant morbidity and mortality, including Pearson syndrome, Kearns-Sayre Syndrome, or Chronic Progressive External Ophthalmoplegia. Therapeutic development has been hindered by limited existing knowledge on mtDNA quality control and a lack of SLSMD animal models. To address this challenge, we utilized the C. elegans heteroplasmic SLSMD strain, uaDf5, to objectively screen for potential therapies. As mitophagy modulation has been implicated in mtDNA homeostasis, we screened a library of mitophagy modulating compounds to determine their comparative effects to rescue mitochondrial unfolded protein (UPRmt) stress induction in in uaDf5 SLSMD worms. Interestingly, Thiamine was discovered to be an effective positive control, significantly reducing mitochondrial stress in this model. Two lead therapeutic candidates from the mitophagy library screen were Hemin and Celastrol (Tripterin). Celastrol is a mitophagy activating anti-inflammatory and metabolic modifying natural product derived compound, that rescued multiple fitness outcomes (thrashing, development, survival) and reduced the mitochondrial stress in uaDf5 animals in a mitophagy-dependent fashion. This study highlights the utility of the uaDf5 worm model to enable preclinical identification of therapeutic candidate leads for SLSMD-based heteroplasmic mtDNA diseases and identifies possible therapeutic candidates that serve as mitophagy modulators to improve health and specifically reduce heteroplasmy levels in SLSMD diseases.

show abstract

The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: A Systematic Review

Cited by 2 publications

References 103 publications

Biomechanical effects of hemin and sildenafil treatments on the aortic wall of chronic-hypoxic lambs

Biomechanical effects of hemin and sildenafil treatments on the aortic wall of chronic-hypoxic lambs

Mitophagy modulation rescues single large-scale mitochondrial DNA deletion (SLSMD) disease symptoms in theC. elegans uaDf5animal model

Contact Info

Product

Resources

About