Changes of Myocardial Functions in Acute Hepatic Porphyrias. Role of Heme Arginate Administration

Kordač, V; Kozàkovà, M.; Martásek, Pavel

doi:10.3109/07853898909149205

Cited by 13 publications

(13 citation statements)

References 3 publications

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“…CoCl 2 , a short-term inducer of HO-1 expression and HO activity, has been reported to have exhib-98 ited antihypertensive effects in the same animal model described above for SnCl 2 (Sacerdoti et al, 1989). Metalloporphyrins, such as heme, heme arginate, and CoPP, are also commonly used to induce HO-1 expression and activity and have been used to normalize blood pressure in animals and humans (Kordac et al, 1989;Martasek et al, 1991). The side effects associated with their use are discussed elsewhere is this review.…”

Section: G Cardiovascular Drugs and Drug Developments Targeting Hemementioning

confidence: 99%

“…Subsequently, others reported that acute and chronic expression of HO-1 decreased vasoconstrictors, such as 20-HETE (Laniado- da Silva et al, 1994), thromboxane synthase activity (Sessa et al, 1989), and COX-2 activity (Abraham, 2003). Heme arginate, or heme, which is used clinically for the treatment of porphyria (Kordac et al, 1989), has been shown to have a beneficial effect on acute induction of HO-1 and lowers blood pressure in hypertensive rats (Schwartz-84 man et Martasek et al, 1991;Wang et al, 2006b). Hemin, a critical component of hemoglobin, is an active ingredient of a biological therapeutic agent approved by the U.S. Food and Drug Administration for the treatment of acute porphyrias.…”

Section: A Increased Levels Of Heme Oxygenase-1 and Heme Oxygenase Amentioning

confidence: 99%

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Pharmacological and Clinical Aspects of Heme Oxygenase

Abraham

Kappas²

2008

Pharmacological Reviews

1,012

988

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Section: G Cardiovascular Drugs and Drug Developments Targeting Hemementioning

confidence: 99%

Section: A Increased Levels Of Heme Oxygenase-1 and Heme Oxygenase Amentioning

confidence: 99%

Pharmacological and Clinical Aspects of Heme Oxygenase

Abraham

Kappas²

2008

Pharmacological Reviews

1,012

988

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“…Hence, the feasibility of heme as a therapy for broad medical indications appears to be questionable and needs further evaluation in clinical practice. A compound with better potential for translation into the clinic might be heme arginate, which appears to be less toxic than heme (Jeney et al, 2002) and is an approved therapy for treatment of hepatic porphyrias in various European countries (Mustajoki et al, 1986; Kordac et al, 1989). Notably, heme arginate was found to up-regulate HO-1 not only in healthy individuals (Doberer et al, 2010), but also in patients receiving deceased donor renal transplants in a recent phase IIB trial (Thomas et al, 2016).…”

Section: Protection Against Heme Toxicity Via Hemopexin and The Heme mentioning

confidence: 99%

Heme as a Target for Therapeutic Interventions

et al. 2017

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Heme is a complex of iron and the tetrapyrrole protoporphyrin IX with essential functions in aerobic organisms. Heme is the prosthetic group of hemoproteins such as hemoglobin and myoglobin, which are crucial for reversible oxygen binding and transport. By contrast, high levels of free heme, which may occur in various pathophysiological conditions, are toxic via pro-oxidant, pro-inflammatory and cytotoxic effects. The toxicity of heme plays a major role for the pathogenesis of prototypical hemolytic disorders including sickle cell disease and malaria. Moreover, there is increasing appreciation that detrimental effects of heme may also be critically involved in diseases, which usually are not associated with hemolysis such as severe sepsis and atherosclerosis. In mammalians homeostasis of heme and its potential toxicity are primarily controlled by two physiological systems. First, the scavenger protein hemopexin (Hx) non-covalently binds extracellular free heme with high affinity and attenuates toxicity of heme in plasma. Second, heme oxygenases (HOs), in particular the inducible HO isozyme, HO-1, can provide antioxidant cytoprotection via enzymatic degradation of intracellular heme. This review summarizes current knowledge on the pathophysiological role of heme for various diseases as demonstrated in experimental animal models and in humans. The functional significance of Hx and HOs for the regulation of heme homeostasis is highlighted. Finally, the therapeutic potential of pharmacological strategies that apply Hx and HO-1 in various clinical settings is discussed.

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“…Stannous chloride (SnCl 2 ) has been reported to lower blood pressure in spontaneously hypertensive rats (Sacerdoti et al, 1989). Metalloporphyrins, such as heme, heme arginate, and CoPP, are also commonly used drugs to induce HO-1 expression and HO activity and have been used to normalize blood pressure in animals and humans (Kordac et al, 1989; Levere et al, 1990; Abraham and Kappas, 2008). However, in discovering the ideal pharmacological drug, one must consider the dose and time of HO-1 induction.…”

Section: Introductionmentioning

confidence: 99%

Physiological significance of heme oxygenase in hypertension

Cao

Inoue

et al. 2009

The International Journal of Biochemistry & Cell Biology

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The last decade has witnessed an explosion in the elucidation of the role that the heme oxygenase system plays in human physiology. This system encompasses not only the heme degradative pathway, including heme oxygenase and biliverdin reductase, but also the products of heme degradation, carbon monoxide, iron, and biliverdin/bilirubin. Their role in diabetes, inflammation, heart disease, hypertension, transplantation, and pulmonary disease are areas of burgeoning research. The research has focused not only on heme itself but also on its metabolic products as well as endogenous compounds involved in a vast number of genetic and metabolic processes that are affected when heme metabolism is perturbed. It should be noted, however, that although the use of carbon monoxide and biliverdin/bilirubin as therapeutic agents has been successful, these agents can be toxic at high levels in tissue, e.g., kernicterus. Care must be used to ensure that when these compounds are used as therapeutic agents their deleterious effects are minimized or avoided. On balance, however, the strategies to target heme oxygenase-1 as described in this review offer promising therapeutic approaches to clinicians for the effective management of hypertension and renal function. The approaches detailed may prove to be seminal in the development of a new therapeutic strategy to treat hypertension.

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Changes of Myocardial Functions in Acute Hepatic Porphyrias. Role of Heme Arginate Administration

Cited by 13 publications

References 3 publications

Pharmacological and Clinical Aspects of Heme Oxygenase

Pharmacological and Clinical Aspects of Heme Oxygenase

Heme as a Target for Therapeutic Interventions

Physiological significance of heme oxygenase in hypertension

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