Metalloporphyrins – An Update

Schulz, Stephanie; Wong, Ronald J.; Vreman, Hendrik J.; Stevenson, David K.

doi:10.3389/fphar.2012.00068

Cited by 76 publications

(65 citation statements)

References 113 publications

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“…They appeared to have significant effects in lowering plasma bilirubin levels, however, were not shown to be superior to phototherapy in treating neonatal jaundice. In addition, treated infants showed a photosensitivity when phototherapy was applied (10). In addition, we have found that zinc deuteroporphyrin bis-glycol (ZnBG) and chromium mesoporphyrin (CrMP) have photo-and chemical toxicity, respectively, despite both being highly potent (26).…”

Section: Articlesmentioning

confidence: 99%

“…or i.m.) (10). The oral route is the most convenient and comfortable means of administration for pharmaceutical products (29), and for Mps, the "first pass effect" allows for a targeted inhibition of HO activity in the liver, the main organ that degrades excessive heme loads in hemolytic conditions.…”

Section: Articlesmentioning

confidence: 99%

“…Their potency is based on their central metal and ring-side chains. Mps have been proposed for use in treating and/or preventing neonatal hyperbilirubinemia for decades (7,9,10). Tin mesoporphyrin (SnMP) has been widely investigated and has even been used in human clinical trials (11)(12)(13).…”

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Inhibition of heme oxygenase activity using a microparticle formulation of zinc protoporphyrin in an acute hemolytic newborn mouse model

et al. 2015

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Background: Increased bilirubin production due to hemolysis can lead to neonatal hyperbilirubinemia. Inhibition of heme oxygenase (HO), the rate-limiting enzyme in heme catabolism, by metalloporphyrins (Mps) may be an ideal preventive strategy for neonatal hemolytic disease. Zinc protoporphyrin (ZnPP) is a naturally occurring Mp, potent, not phototoxic, with minimal HO-1 upregulation, but is not orally absorbed. Recently, we designed a lipid-based ZnPP formulation (ZnPP-Lipid), which is orally absorbed by newborn mice. Here, we evaluated the efficacy of ZnPP-Lipid in heme-loaded newborn mice, a model analogous to hemolytic infants. Methods: After 24 h of heme administration (30 µmol/kg s.c.), 4-d-old mice were given 30 µmol ZnPP-Lipid/kg via intragastric injections. After 3 h, liver and brain HO activity were measured. HO-1 upregulation was assessed by determinations of HO-1 protein, promoter activity, and mRNA by Western blot, in vivo bioluminescence imaging, and RT-PCR, respectively. results: After heme loading, liver HO activity significantly increased ~1.6-fold, which was inhibited in a dose-dependent manner by ZnPP-Lipid. A dose of 30 µmol/kg returned activity to control levels. Brain HO activity was not inhibited. No significant increases in liver and brain HO-1 protein, promoter activity, and mRNA were observed. conclusion: ZnPP-Lipid is effective and thus has potential for treating neonatal hyperbilirubinemia due to hemolysis.

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Section: Articlesmentioning

confidence: 99%

Section: Articlesmentioning

confidence: 99%

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Inhibition of heme oxygenase activity using a microparticle formulation of zinc protoporphyrin in an acute hemolytic newborn mouse model

et al. 2015

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“…The effects of bilirubin vary with age (Dennery, 2012), and metalloporphyrins have been suggested to reduce excessive hyperbilirubinemia and brain damage in newborns (Schulz et al, 2012).…”

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The role of bile pigments in health and disease: effects on cell signaling, cytotoxicity and cytoprotection

2012

Frontiers Research Topics

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“…reported that metalloporphyrins interact with many heme-containing enzyme systems, including soluble guanylyl cylase (sGC), nitric oxide synthase (NOS), and cytochrome P450 (CYP450) [247].…”

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confidence: 99%

Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

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The prevalence of obesity is growing at an alarming rate worldwide, and current therapies have limited benefits. Therefore, it is essential to increase our understanding of the underlying mechanisms so that new strategies can be developed to reduce the incidence of obesity related diseases. Adiponectin is an adipocyte-derived hormone that regulates glucose and lipid metabolism via direct and indirect mechanisms and has anti-inflammatory, anti-diabetic, anti-atherogenic and cardioprotective properties. Hypoadiponectinemia is implicated in the aetiology of obesity-related diseases making strategies to increase circulating adiponectin levels therapeutically attractive.Emerging evidence, predominantly from preclinical studies, suggests induction of heme-oxygenase-1 (HO-1) increases adiponectin production concomitant with decreased inflammatory tone prompting the proposal of a "HO-1 -adiponectin axis." However, the underlying mechanisms of increased adiponectin production via HO-1 induction are poorly defined; indeed a direct relationship has not been demonstrated. Thus, the overarching aim of this thesis is to investigate the effects of HO-1 induction on adiponectin production as well as adipocyte and adipose tissue remodelling and metabolic parameters using cellular and mouse models.Initial studies were designed to characterize the direct effect of HO-1 induction on adiponectin production. We found that treatment with the widely used HO-1 inducer cobalt protoporphyrin (CoPP) or hemin for 24-48 h increased HO-1 expression and activity without affecting adiponectin expression and secretion, in human mature adipocyte under a variety of experimental scenarios.Treatment of adipocytes with TNFα reduced adiponectin production and induced pro-inflammatory cytokines production. HO-1 induction failed to reverse these effects. These results do not support a direct HO-1 -adiponectin axis.However, literature suggests that chronic induction of HO-1 via CoPP administration throughout differentiation, promotes adiponectin secretion, albeit in the context of reduced adipogenesis. While our previous findings argued against the existence of a direct "HO-1 -adiponectin axis," they did not address the potential effects of chronic induction of HO-1 on adiponectin production. Thus, we extended our study to characterise the effects of chronic HO-1 induction throughout differentiation of human preadipocytes. In this study we demonstrate that chronic induction of HO-1 with CoPP or hemin throughout differentiation results in dose-dependent inhibition of adipogenesis and adiponectin production as well as induction of additional NRF2 target genes. Co-treatment with SnMP (HO-1 activity inhibitor) and HO-1 siRNA did not prevent these effects. These findings suggest that the chronic treatment with CoPP or hemin inhibits adipogenesis and adiponectin production potentially by a HO-1-independent mechanism that may be downstream of NRF2.iii However, our results contradict the majority of reports in the literature. One possibility is that the ...

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Metalloporphyrins – An Update

Cited by 76 publications

References 113 publications

Inhibition of heme oxygenase activity using a microparticle formulation of zinc protoporphyrin in an acute hemolytic newborn mouse model

Inhibition of heme oxygenase activity using a microparticle formulation of zinc protoporphyrin in an acute hemolytic newborn mouse model

The role of bile pigments in health and disease: effects on cell signaling, cytotoxicity and cytoprotection

Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

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