Page last updated: 2024-12-06

heme

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ferroheme : Any iron(II)--porphyrin coordination complex. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

ferroheme b : Heme b in which the iron has oxidation state +2. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

heme : A heme is any tetrapyrrolic chelate of iron. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID53356659
CHEBI ID17627
MeSH IDM0010066

Synonyms (27)

Synonym
fe(ppix)
ferroprotoheme
protoferroheme
[fe(ppix)]
[3,7,12,17-tetramethyl-8,13-divinylporphyrin-2,18-dipropanoato(2-)]iron(ii)
CHEBI:17627
(protoporphyrinato)iron(ii)
iron protoporphyrin
ferrous protoheme ix
reduced hematin
HEM ,
iron protoporphyrin ix
ferrous protoheme
iron(ii) protoporphyrin ix
ferroheme
protoporphyrin ix containing fe
protohaem
ferroprotoporphyrin
haem
14875-96-8
heme
protoheme ,
ferroheme b
protoheme ix
ferroprotoporphyrin ix
(protoporphyrinato)iron
[3,3'-(7,12-diethenyl-3,8,13,17-tetramethylporphyrin-2,18-diyl-kappa~4~n~21~,n~22~,n~23~,n~24~)dipropanoato(2-)]iron

Research Excerpts

Toxicity

Heme-hemopexin can protect against the potentially toxic effects of heme. Treatment of mice for 37 days with AZT produced anemia and leukopenia. Combined treatment with heme abrogated some of the toxic effects.

ExcerptReferenceRelevance
" As much as 1% of the working population may have a significantly increased lead absorption with possible adverse effects."( Widening perspectives of lead toxicity. A review of health effects of lead exposure in adults.
Grandjean, P, 1978
)
0.26
" Thus, this commercially important and widely distributed chemical with high acute toxicity is not considered to be teratogenic in hamsters, and it produces embryotoxicity only at dose rates that result in toxic signs in the dams."( Embryotoxic effects of sodium azide infusions in the Syrian hamster.
Ferm, VH; Kruszyna, H; Kruszyna, R; Sana, TR; Smith, RP; Wilcox, DE, 1990
)
0.28
"01 microM) was found to be toxic to bone marrow colony growth."( Role of heme metabolism in AZT-induced bone marrow toxicity.
Abraham, NG; Levere, RD; Lutton, JD; Mathew, A, 1990
)
0.28
" However, the porphyrin precursor delta-aminolevulinic acid (delta-ALA) is not toxic up to millimolar concentrations within a 30-h time period."( Some aspects of porphyrin neurotoxicity in vitro.
Kennedy, JC; Riopelle, RJ, 1982
)
0.26
" We reasoned that hemin, previously shown to both enhance BFU-E proliferation and accelerate erythroid maturation, might bring about differentiation of this large SCF-induced pool of BFU-E and further protect BFU-E from AZT's toxic effect."( Amelioration of azidothymidine-induced erythroid toxicity by hemin and stem cell factor in immune-suppressed mice.
Chen, RB; Hamburger, AW, 1994
)
0.29
" Treatment of mice for 37 days with AZT produced anemia and leukopenia, whereas combined treatment with heme abrogated some of the toxic effects which were apparent even 2 weeks after cessation of treatment."( Long-term bone marrow stromal and hemopoietic toxicity to AZT: protective role of heme and IL-1.
Abraham, NG; Argani, I; Chertkov, JL; Jiang, S; Kappas, A; Levere, RD; Lutton, JD; Staudinger, R, 1993
)
0.29
" We examined whether heme oxygenase is induced, and the functional significance of such induction, in two in vivo models of oxidant-induced toxic nephropathy, namely, cisplatin and gentamicin nephropathies; nephrotoxicity in these models is not dependent on the delivery of a burden of heme proteins to the kidney as occurs in the glycerol model."( Induction of heme oxygenase in toxic renal injury: a protective role in cisplatin nephrotoxicity in the rat.
Agarwal, A; Alam, J; Balla, J; Croatt, AJ; Nath, KA, 1995
)
0.29
" Free but not protein-bound ferric iron and heme exacerbated the toxic effect."( Heme-mediated reactive oxygen species toxicity to retinal pigment epithelial cells is reduced by hemopexin.
Handy, I; Hunt, RC; Smith, A, 1996
)
0.29
" However, when the Fe content of the cereal-milk formula was doubled by supplementation with bovine blood, the adverse effects on the digestive utilization of Ca, and especially of Mg, were palliated, the concentration of these two minerals in the organs investigated increased, and the overall Fe status improved in Fe-deficient rats."( Supplementation of a cereal-milk formula with haem iron palliates the adverse effects of iron deficiency on calcium and magnesium metabolism in rats.
Alférez, MJ; Barrionuevo, M; Campos, MS; Gómez-Ayala, AE; Hartiti, S; Lisbona, F; López-Aliaga, I; Pallarés, I, 1996
)
0.29
"Numerous pathologies may involve toxic side effects of free heme and heme-derived iron."( Pro-oxidant and cytotoxic effects of circulating heme.
Balla, G; Balla, J; Eaton, JW; Jeney, V; Varga, Z; Vercellotti, GM; Yachie, A, 2002
)
0.31
" The adverse effects of CO poisoning may be more widespread because of unreported situations and delayed neurologic effects, which may be linked to CO exposure."( Metabolic modulation of carbon monoxide toxicity.
Omaye, ST, 2002
)
0.31
" Heme offers severe toxic effects to kidney, liver, central nervous system and cardiac tissue."( Free heme toxicity and its detoxification systems in human.
Bandyopadhyay, U; Kumar, S, 2005
)
0.33
"Occupational and environmental exposures to lead (Pb), one of the toxic metal pollutants, is of global concern."( Lead hepatotoxicity & potential health effects.
Mudipalli, A, 2007
)
0.34
" Taken together, these results have led to the suggestion that hrtAB encodes an efflux system responsible for relieving the toxic effects of accumulated heme."( Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response.
Anderson, KL; Bagaley, D; Dunman, PM; Joyce, R; Kuechenmeister, L; Skaar, EP; Stauff, DL; Torres, VJ, 2008
)
0.35
" Many drug oxidation reactions are partially uncoupled, leading to the formation of highly toxic reactive oxygen species, which can cause unpredictable toxic effects on the cell."( New cytochrome P450 mechanisms: implications for understanding molecular basis for drug toxicity at the level of the cytochrome.
Shakunthala, N, 2010
)
0.36
" Paradoxically, the high redox potential of heme makes it a liability, as heme is toxic at high concentrations."( Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens.
Anzaldi, LL; Skaar, EP, 2010
)
0.36
" The present study was designed to find a Ca supplementation with no adverse effect, by testing several doses and types of Ca salts."( Calcium carbonate suppresses haem toxicity markers without calcium phosphate side effects on colon carcinogenesis.
Allam, O; Bahuaud, D; Corpet, DE; Naud, N; Pierre, FH; Taché, S, 2011
)
0.37
" The level of methemoglobin in the bloodstream is an worthy biomarker, predictor and precursor of environmental toxics' adverse effects on the mother and fetus, and can indirectly explain the unrecognized level of fetal methemoglobin."( Pregnancy loss and maternal methemoglobin levels: an indirect explanation of the association of environmental toxics and their adverse effects on the mother and the fetus.
Haller, H; Micovic, V; Mohorovic, L; Petrovic, O, 2010
)
0.36
" There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-d-β-acetylglucosaminidase in urine), but without statistical significance."( δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system.
Bergdahl, IA; Broberg, K; Guo, W; Jin, T; Lei, L; Liang, Y; Nilsson, J; Skerfving, S; Tian, L; Zheng, G, 2011
)
0.37
" Here, we tested whether Hx could be used as a therapeutic tool to counteract heme toxic effects on the cardiovascular system in hemolytic diseases."( Hemopexin therapy improves cardiovascular function by preventing heme-induced endothelial toxicity in mouse models of hemolytic diseases.
Altruda, F; Cimino, J; De Franceschi, L; Ghigo, A; Hirsch, E; Silengo, L; Tolosano, E; Townes, T; Vinchi, F, 2013
)
0.39
" In conclusion, though increased plasma heme does not play a role in triggering or aggravating MH, heme release appears as a relevant toxic mediator leading to renal impairment, primarily through PTC endothelial dysfunction rather than direct tubular toxicity."( Plasma heme-induced renal toxicity is related to a capillary rarefaction.
Bilbault, H; Estournet, C; Girshovich, A; Hammoudi, N; Haymann, JP; Jouanneau, C; Letavernier, E; Lionnet, F; Perez, J; Placier, S; Tabibzadeh, N; Vandermeersch, S, 2017
)
0.46
"Nanoparticles (NPs) due to their small size and high surface area induce remarkable adverse effects on the biological systems."( ROS-mediated heme degradation and cytotoxicity induced by iron nanoparticles: hemoglobin and lymphocyte cells as targets.
Attar, F; Falahati, M; Hadadi, Z; Mirzaei, S; Mousavi, SE; Rezayat, SM; Saboury, AA; Tajik, A; Zargar, SS, 2018
)
0.48
"Hexachloronaphthalenes (HxCNs) are the most toxic congeners of polychlorinated naphthalenes, a group of compounds lately included into the list of persistent organic pollutants (POPs)."( The effects of hexachloronaphthalene on selected parameters of heme biosynthesis and systemic toxicity in female wistar rats after 90-day oral exposure.
Bruchajzer, E; Darago, A; Domeradzka-Gajda, K; Kilanowicz, A; Klimczak, M; Kuzajska, K; Stepnik, M, 2018
)
0.48
" This is safe redox-metal trafficking, without oxidative stress, as iron released from heme catabolism by HOs as well as copper taken up with heme-hemopexin move through the cell."( Safe coordinated trafficking of heme and iron with copper maintain cell homeostasis: modules from the hemopexin system.
Davis, T; Eskew, JD; Smith, A; Sung, L; Vanacore, R, 2019
)
0.51
" Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium."( Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit.
Boudhabhay, I; Frimat, M; Roumenina, LT, 2019
)
0.51
"Serum albumin binds avidly to heme to form heme-serum albumin complex and can protect against the potentially toxic effects of heme."( Formation of a bovine serum albumin diligand complex with rutin for the suppression of heme toxicity.
Lu, N; Luo, M; Sui, Y; Tian, R, 2020
)
0.56
" The acute onset of toxicity and CN's mg/Kg LD50 (μM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN."( Acute toxicity of cyanide in aerobic respiration: Theoretical and experimental support for murburn explanation.
Gideon, DA; Jacob, VD; Manoj, KM; Pakshirajan, K; Parashar, A; Ramasamy, S; Soman, V, 2020
)
0.56
" A series of studies to investigate the effects of flumioxazin have revealed that developmental toxicity is caused in rats but not in rabbits, and the adverse effects are not likely to occur in humans."( Lack of human relevance for rat developmental toxicity of flumioxazin is revealed by comparative heme synthesis assay using embryonic erythroid cells derived from human and rat pluripotent stem cells.
Asano, K; Fukuda, T; Kitamoto, S; Otani, M; Takahashi, Y; Tomigahara, Y; Ueno, M, 2022
)
0.72
" These treatment methods involvevarious adverse reactions; therefore, it remains necessary to explore new treatment methods."( Enhancement of the cytotoxic effect of dihydroartemisinin in high-risk human papillomavirus-infected cells by aminolevulinic acid via the Bax/Bcl-2-caspase pathway.
Che, Q; Li, C; Lu, H; Wang, Q; Zeng, K, 2022
)
0.72
" The results showed that HI had no adverse effects on any of the examined parameters."( A 13-week subchronic toxicity study of heme iron in SD rats.
Akane, H; Matsushita, K; Morikawa, T; Ogawa, K; Toyoda, T, 2023
)
0.91
"Heme is a fundamental molecule for several biological processes, but when released in the extracellular space such as in hemolytic diseases, it can be toxic to cells and tissues."( Safety and feasibility of the gene transfer of hemopexin for conditions with increased free heme.
Borba-Junior, IT; Costa, FF; de Lima, F; de Moraes, CRP; De Paula, EV; Hounkpe, BW, 2023
)
0.91

Pharmacokinetics

ExcerptReferenceRelevance
"The pharmacokinetic parameters of ranitidine were studied following administration of a single intravenous dose in 9 critically ill infants."( Pharmacokinetics of ranitidine in critically ill infants.
Brundage, RC; Gillette, PC; O'Neal, W; Reigart, JR; Wiest, DB; Yost, RL, 1989
)
0.28
" mean elimination half-life of 10."( Pharmacokinetics of intravenously administered haem arginate.
Mustajoki, P; Tenhunen, R; Tokola, O; Volin, L, 1986
)
0.27
"Two chemotypes were examined in vitro with CYPs 3A4 and 2C19 by molecular docking, metabolic profiles, and intrinsic clearance deuterium isotope effects with specifically deuterated form to assess the potential for enhancement of pharmacokinetic parameters."( Deuterium isotope effects in drug pharmacokinetics II: Substrate-dependence of the reaction mechanism influences outcome for cytochrome P450 cleared drugs.
Coffey, SB; Futatsugi, K; Orr, STM; Piotrowski, DW; Sun, H; Vaz, ADN; Warmus, JS; Wolford, AC; Zhang, Y, 2018
)
0.48

Compound-Compound Interactions

ExcerptReferenceRelevance
" We developed a gas-phase resonance Raman spectroscopy combined with IR-laser ablation of a droplet beam, which allowed us to elucidate local structures around chromophores in gas-phase proteins and DNAs."( Gas-Phase Resonance Raman Spectroscopy Combined with IR-Laser Ablation of a Droplet Beam: Local Structural Analysis of Myoglobin.
Asami, H; Kawauchi, N; Kitazaki, A; Kohno, JY, 2020
)
0.56

Bioavailability

Beef protein was found to enhance the bioavailability of nonheme iron in the rat. A heme-iron concentrate product derived from swine hemoglobin was used to enrich the chocolate-flavored filling of biscuits. The bioavailability and utilization of porphyrin-bound iron, specifically heme, by marine microorganisms have rarely been examined.

ExcerptReferenceRelevance
" The human requirement for iron, bioavailability of heme and nonheme iron, and amounts of heme and nonheme iron in the diet are individually estimated after reviewing the relevant literature in Sections II, III, and IV, respectively."( Contributions of heme and nonheme iron to human nutrition.
Carpenter, CE; Mahoney, AW, 1992
)
0.28
" Thus diets rich in enhancers of non-haem iron absorption, chiefly meat and/or ascorbic acid, have high iron bioavailability (about 3 mg d-1) while diets in which inhibitors, such as polyphenols and phytates, predominate are poor sources of iron (less than 1 mg d-1)."( Nutritional iron requirements and food iron absorption.
Baynes, RD; Bothwell, TH; MacFarlane, BJ; MacPhail, AP, 1989
)
0.28
" The bioavailability of non heme iron is influenced by the composition of the diet."( [The role of iron as a deficient element].
Schümann, K, 1989
)
0.28
" However, when this meal was both modified to promote bioavailability and supplemented with iron, absorption of nonheme iron was significantly elevated."( Food iron absorption in idiopathic hemochromatosis.
Cook, JD; Lynch, SR; Skikne, BS, 1989
)
0.28
"Beef protein was found to enhance the bioavailability of nonheme iron in the rat."( The enhancement of nonheme iron bioavailability by beef protein in the rat.
Godber, JS; Gordon, DT, 1989
)
0.28
" To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes."( Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation.
Hebbel, RP; Kuross, SA, 1988
)
0.27
"The degree to which inhibitors of zinc bioavailability actually influence the zinc status of humans who consume usual meals and diets is not known."( Competitive interaction of iron and zinc in the diet: consequences for human nutrition.
Solomons, NW, 1986
)
0.27
" Haem arginate administered in high doses prior to oral propranolol did not alter the bioavailability of the latter."( Barbiturate and ethanol sleeping times and pharmacokinetics of propranolol in mice after intravenous administration of haem arginate.
Tokola, O, 1987
)
0.27
" The amount of meat in a meal is the only bioavailability factor known to influence absorption of heme iron."( An overview of current information on bioavailability of dietary iron to humans.
Morris, ER, 1983
)
0.27
" Heme iron present in hemoglobin and myoglobin, is well absorbed and is relatively unaffected by diet composition."( Nutritional significance of interactions between iron and food components.
Amar, M; Calvo, E; Chadud, P; Hertrampf, E; Llaguno, S; Olivares, M; Pizarro, F; Stekel, A, 1983
)
0.27
" Heme iron, derived from hemoglobin and myoglobin, is well absorbed and relatively little affected by other foods eaten in the same meal."( Interaction of vitamin C and iron.
Cook, JD; Lynch, SR, 1980
)
0.26
" The amount of iron absorbed from a meal depends not only on its contents of heme and nonheme iron and on various dietary factors affecting the bioavailability but also on the iron status of the subjects studied."( Bioavailable nutrient density: a new concept applied in the interpretation of food iron absorption data.
Hallberg, L, 1981
)
0.26
" Several factors to consider in the choice of strategy are discussed such as the importance of the bioavailability of the diet for the efficacy of iron fortification, the choice of vehicle for iron fortification that is compatible with the iron compound used, the feasibility to increase the bioavailability of the dietary iron by modification of the composition of the diet and the short time available in pregnancy to ensure a sufficient supply of the extra iron needed limiting the effective measures available to supplementation with iron tablets."( Prevention of iron deficiency.
Hallberg, L, 1994
)
0.29
"Aside from the well known alteration of Fe status in Fe deficiency, this condition has also a negative effect on the bioavailability of Ca and Mg."( Supplementation of a cereal-milk formula with haem iron palliates the adverse effects of iron deficiency on calcium and magnesium metabolism in rats.
Alférez, MJ; Barrionuevo, M; Campos, MS; Gómez-Ayala, AE; Hartiti, S; Lisbona, F; López-Aliaga, I; Pallarés, I, 1996
)
0.29
" Our objectives were to describe the dietary information, analytical steps, and computer algorithms needed for iron bioavailability adjustments and to demonstrate the effects of various dietary factors on calculated iron absorption."( Adjustment of iron intake for dietary enhancers and inhibitors in population studies: bioavailable iron in rural and urban residing Russian women and children.
Chakraborty, H; Kohlmeier, L; Mendez, M; Robinson, DT; Tseng, M, 1997
)
0.3
" Taking into account a zinc absorption rate from meat of about 20-36%, the daily requirements for absorbed zinc were covered to 32-56%."( Available iron and zinc in major lean meat cuts and their contribution to the recommended trace element supply in Switzerland.
Kreuzer, M; Leonhardt, M; Wenk, C, 1997
)
0.3
" Our results suggest that in typical Western-style diets, a small number of dietary factors probably modulate the bioavailability of dietary iron and influence the accumulation of iron stores."( Dietary determinants of iron stores in a free-living elderly population: The Framingham Heart Study.
Dallal, GE; Fleming, DJ; Jacques, PF; Tucker, KL; Wilson, PW; Wood, RJ, 1998
)
0.3
" Bioavailability was assessed by chemical balance using carmine to mark the beginning and end of the faecal collection."( Evaluation of iron bioavailability in infant weaning foods fortified with haem concentrate.
Eagles, J; Fairweather-Tait, S; Fox, T; Martinez, C, 1998
)
0.3
"Haem iron concentrate appears to be a highly bioavailable form of iron when added to infant weaning foods."( Evaluation of iron bioavailability in infant weaning foods fortified with haem concentrate.
Eagles, J; Fairweather-Tait, S; Fox, T; Martinez, C, 1998
)
0.3
" Due to predominantly vegetarian diets that reduce the bioavailability of food iron drastically, deficiency states are most widely distributed in developing countries."( Iron supplementation.
Elsenhans, B; Mäurer, A; Schümann, K, 1998
)
0.3
" Dietary heme iron could not prevent postgastrectomy anemia itself, but fructooligosaccharides improve bioavailability of not only non-heme iron such as iron-citrate, but also heme-iron in rats."( Dietary heme iron does not prevent postgastrectomy anemia but fructooligosaccharides improve bioavailability of heme iron in rats.
Adachi, T; Ohta, A; Sakai, K; Takasaki, M; Tokunaga, T; Uehara, M, 1999
)
0.3
" High metabolic lability usually leads to poor bioavailability and high clearance."( Role of drug metabolism in drug discovery and development.
Kumar, GN; Surapaneni, S, 2001
)
0.31
"Dietary low iron bioavailability intake is an important causation factor of iron deficiency anemia in Asian countries including Thailand."( Iron bioavailability in Thai diets.
Boontaveeyuwat, N; Chitplee, S; Kwanbunjan, K; Saereesuchart, W; Sittisingh, U; Songchitsomboon, S, 2002
)
0.31
"Although the deleterious vasoconstrictive effects of cell-free, hemoglobin-based blood substitutes have been appreciated, the systemic effects of chronic hemolysis on nitric oxide bioavailability have not been considered or quantified."( Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease.
Cannon, RO; Gladwin, MT; Hogg, N; Reiter, CD; Schechter, AN; Tanus-Santos, JE; Wang, X, 2002
)
0.31
"The bioavailability of iron from ferrous sulfate (FeII-S), heme iron prepared from hemoglobin (HIP), and bonito dark muscle (BDM) was assessed in anemic rats using a hemoglobin regeneration efficiency (HRE) method."( Evaluation of iron bioavailability from bonito dark muscle using anemic rats.
Doi, M; Ebihara, K; Kishida, T; Matsumoto, J; Mori, N, 2003
)
0.32
" Studies in the 1970s and the 1980s of metal bioavailability and impacts of metals and metalloids were driven by the process of abatement of lead in the environment."( A commentary on the impacts of metals and metalloids in the environment upon the metabolism of drugs and chemicals.
Moore, MR, 2004
)
0.32
" Whether eNOS catalyzes nitric oxide biosynthesis or the synthesis of reactive oxygen species such as superoxide, hydrogen peroxide, and peroxynitrite is dictated by the bioavailability of tetrahydrobiopterin (BH(4)) and L-arginine during eNOS catalysis."( Three different oxygen-induced radical species in endothelial nitric-oxide synthase oxygenase domain under regulation by L-arginine and tetrahydrobiopterin.
Berka, V; Palmer, G; Tsai, AL; Wu, G; Yeh, HC, 2004
)
0.32
" In light of these observations, we have proposed a model of AD pathobiology in which intracellular A beta complexes with free heme, thereby decreasing its bioavailability (e."( A role for heme in Alzheimer's disease: heme binds amyloid beta and has altered metabolism.
Atamna, H; Frey, WH, 2004
)
0.32
"Impaired microvascular function during myocardial ischemia and reperfusion is associated with recruitment of polymorphonuclear neutrophils (PMN) and has been attributed to decreased bioavailability of nitric oxide (NO)."( Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion.
Baldus, S; Berger, J; Duchstein, HJ; Eiserich, JP; Freeman, BA; Goldmann, B; Heitzer, T; Helmchen, U; Lau, D; Meinertz, T; Mollnau, H; Münzel, T; Ortak, M; Petri, S, 2004
)
0.32
"0 were subjected to 3 h exposure to microwave field (with a specific absorption rate of 51 +/- 1 mW/g); the heme site refolding has been followed by measuring the molecular absorption in the Soret spectral region and the data were fitted to a bi-exponential model."( Non-thermal effects of electromagnetic fields at mobile phone frequency on the refolding of an intracellular protein: myoglobin.
Abbruzzese, A; Bismuto, E; Caraglia, M; d'Ambrosio, G; Mancinelli, F; Massa, R, 2004
)
0.32
" For that reason, the aim of this paper is to accurately review all investigations reported in the past decade related to dietetic factors that influence the bioavailability of different iron forms."( Iron availability: An updated review.
López, MA; Martos, FC, 2004
)
0.32
" This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in vivo (oral ID(50) of 25 micromol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0."( Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine.
Alizadeh-Shekalgourabi, S; Auparakkitanon, S; Carr, P; Dascombe, MJ; Drew, MG; Dyas, AM; Evans, PG; Ismail, FM; Lloyd, M; Morris, H; Moule, WA; Wilairat, P, 2005
)
0.33
" Two experiments tested basal meals with low iron bioavailability and 360 mg Ca (n = 15) or with high iron bioavailability and 60 mg Ca (n = 12)."( Inhibitory effects of dietary calcium on the initial uptake and subsequent retention of heme and nonheme iron in humans: comparisons using an intestinal lavage method.
Hunt, JR; Roughead, ZK; Zito, CA, 2005
)
0.33
" The primary reason is the high bioavailability of heme iron, but it is also known from radiolabeled single-meal feeding studies in humans that muscle tissue facilitates absorption of nonheme iron."( Meat consumption in a varied diet marginally influences nonheme iron absorption in normal individuals.
Cook, JD; Hurrell, RF; Reddy, MB, 2006
)
0.33
" Use of mucin may also enable more complete assessment of iron bioavailability from large molecular weight forms of Fe such as heme and ferritin Fe."( Moving toward a more physiological model: application of mucin to refine the in vitro digestion/Caco-2 cell culture system.
Glahn, R; Jin, F; Welch, R, 2006
)
0.33
" Additionally, excessive production of Abeta in AD brain may bind to and restrict the bioavailability of regulatory heme, creating a condition of heme-deficiency."( Heme binding to Amyloid-beta peptide: mechanistic role in Alzheimer's disease.
Atamna, H, 2006
)
0.33
"A diet with high iron bioavailability protects children from anemia and can be used as an intervention measure by basic health services and by the municipal departments of children's education."( Iron bioavailability as a protective factor against anemia among children aged 12 to 16 months.
Bortolini, GA; Vitolo, MR,
)
0.13
" We now report the use of quercetin-hamster serum albumin combination to increase the bioavailability of quercetin."( Albumin-quercetin combination offers a therapeutic advantage in the prevention of reduced survival of erythrocytes in visceral leishmaniasis.
Biswas, D; Biswas, T; Ray, M; Sen, G,
)
0.13
"The objective of this work was to evaluate the bioavailability of heme iron added to biscuit filling."( Bioavailability of heme iron in biscuit filling using piglets as an animal model for humans.
González-Rosendo, G; Polo-Pozo, J; Quintero-Gutiérrez, AG; Rodríguez-Jerez, JJ; Sánchez-Muñoz, J, 2008
)
0.35
"A heme-iron concentrate product derived from swine hemoglobin was used to enrich the chocolate-flavored filling of biscuits and the bioavailability of this source of heme-iron was assessed in adolescent girls."( Bioavailability of a heme-iron concentrate product added to chocolate biscuit filling in adolescent girls living in a rural area of Mexico.
González-Rosendo, G; Polo, J; Puga-Díaz, R; Quintero-Gutiérrez, AG; Reyes-Navarrete, EG; Rodríguez-Jerez, JJ, 2010
)
0.36
"To study heme iron bioavailability and the role of dietary protein (animal and vegetable) on iron uptake using an in vitro model (Caco-2 cell line)."( Effect of dietary protein on heme iron uptake by Caco-2 cells.
Arredondo, M; de Romaña, DL; Flores, S; Pizarro, F; Villarroel, P, 2011
)
0.37
"Curcumin has been shown to have anti malarial activity, but poor bioavailability and chemical instability has hindered its development as a drug."( Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice.
Akhtar, F; Kar, SK; Rizvi, MM,
)
0.13
"An increase in production of reactive oxygen species resulting in a decrease in nitric oxide bioavailability in the endothelium contributes to many cardiovascular diseases, and these reactive oxygen species can oxidize cellular macromolecules."( Superoxide induces endothelial nitric-oxide synthase protein thiyl radical formation, a novel mechanism regulating eNOS function and coupling.
Chen, CA; Chen, YR; Druhan, LJ; Lin, CH; Wang, TY; Zweier, JL, 2011
)
0.37
" Heme iron has high bioavailability and a low capacity to cause gastrointestinal side effects."( Heme iron-based dietary intervention for improvement of iron status in young women.
Brün, B; Hoppe, M; Hulthén, L; Larsson, MP; Moraeus, L, 2013
)
0.39
"HO1 (haem oxygenase 1) and Fpn (ferroportin) are key proteins for iron recycling from senescent red blood cells and therefore play a major role in controlling the bioavailability of iron for erythropoiesis."( Ferroportin expression in haem oxygenase 1-deficient mice.
Bierła, J; Canonne-Hergaux, F; Dziaman, T; Krzeptowski, W; Lenartowicz, M; Lipiński, P; Pietrzak, P; Starzyński, RR; Styś, A; Willemetz, A, 2013
)
0.39
"7 g mucin on 5 mg heme iron bioavailability on days 1, 2, 14, and 15, respectively."( Effect of trypsin and mucin on heme iron bioavailability in humans.
Brito, A; Cediel, G; Flores, S; Gaitán, D; Olivares, M; Pizarro, F, 2012
)
0.38
" Iron uptake provides a significant challenge given its limited bioavailability and need to be transported across the bacterial cell wall and membranes."( Extracellular heme uptake and the challenges of bacterial cell membranes.
Smith, AD; Wilks, A, 2012
)
0.38
" The discussion of iron properties will center on the speciation and localization of intracellular iron as well as the cellular and molecular mechanisms for coping with both low iron bioavailability and iron toxicity."( The iron metallome in eukaryotic organisms.
Dlouhy, AC; Outten, CE, 2013
)
0.39
"The bioavailability and utilization of porphyrin-bound iron, specifically heme, by marine microorganisms have rarely been examined."( Utilization of heme as an iron source by marine Alphaproteobacteria in the Roseobacter clade.
Barbeau, KA; Hogle, SL; Roe, KL, 2013
)
0.39
"The bioavailability of terminal electron acceptors (TEAs) and other substrates affects the efficiency of subsurface bioremediation."( Survival during long-term starvation: global proteomics analysis of Geobacter sulfurreducens under prolonged electron-acceptor limitation.
Bansal, R; Brantley, SL; Helmus, RA; Liermann, LJ; Stanley, BA; Tien, M; Zhu, J, 2013
)
0.39
" In addition, compared with FeSO4, higher Fe bioavailability and fewer side effects were observed."( Effects of heme iron enriched peptide on iron deficiency anemia in rats.
Chen, LQ; Tang, N; Zhuang, H, 2014
)
0.4
" In the cell the bioavailability of iron for the two main iron biological pathways--heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S])--is mainly regulated by the IRP/IRE posttranscriptional system."( [Heme metabolism as an integral part of iron homeostasis].
Gajowiak, A; Lipiński, P; Staroń, R; Starzyński, RR; Styś, A, 2014
)
0.4
"To determine the effect of phytic acid, tannic acid and pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium."( Effect of phytic acid, tannic acid and pectin on fasting iron bioavailability both in the presence and absence of calcium.
Andrews, M; Arredondo, M; Briones, L; Brito, A; Jaramillo, Á; Olivares, M; Pizarro, F, 2015
)
0.42
"The geometric means of iron bioavailability (range±1SD) for iron alone, iron with phytic acid, iron with tannic acid, and iron with citrus pectin were 25."( Effect of phytic acid, tannic acid and pectin on fasting iron bioavailability both in the presence and absence of calcium.
Andrews, M; Arredondo, M; Briones, L; Brito, A; Jaramillo, Á; Olivares, M; Pizarro, F, 2015
)
0.42
"Tannic acid decreases the fasting bioavailability of non-heme iron, however this effect did not exist in the presence of calcium."( Effect of phytic acid, tannic acid and pectin on fasting iron bioavailability both in the presence and absence of calcium.
Andrews, M; Arredondo, M; Briones, L; Brito, A; Jaramillo, Á; Olivares, M; Pizarro, F, 2015
)
0.42
" Because of its limited bioavailability in the host, bacteria have adapted several strategies to acquire iron during infection."( Heme interplay between IlsA and IsdC: Two structurally different surface proteins from Bacillus cereus.
Abi-Khalil, E; André-Leroux, G; Bou-Abdallah, F; Kallassy, M; Lereclus, D; Nielsen-Leroux, C; Segond, D; Terpstra, T, 2015
)
0.42
" A highly bioavailable heme iron ingredient was selected to fortify a chocolate cream used to fill sandwich-type cookies."( Oxidative stability of a heme iron-fortified bakery product: Effectiveness of ascorbyl palmitate and co-spray-drying of heme iron with calcium caseinate.
Alemán, M; Bou, R; Codony, R; Guardiola, F; Polo, J; Tres, A, 2016
)
0.43
" Study 1: the bioavailability of heme Fe from Hb was similar to heme only (∼13."( The effect of proteins from animal source foods on heme iron bioavailability in humans.
Arredondo, M; Brito, A; Flores, S; Olivares, M; Pizarro, F; Valenzuela, C; Weinborn, V, 2016
)
0.43
" Moreover, LmHR1 levels modulated by its overexpression or the abrogation of an LmHR1 allele correlate with the mitochondrial bioavailability of heme from lysosomal hemoglobin."( Trypanosomatid parasites rescue heme from endocytosed hemoglobin through lysosomal HRG transporters.
Cabello-Donayre, M; Campos-Salinas, J; Estévez, AM; Gálvez, FJ; Malagarie-Cazenave, S; Martínez-García, M; Orrego, LM; Pérez-Victoria, JM; Pineda-Molina, E; Rodríguez-Martínez, A; Sánchez-Cañete, MP, 2016
)
0.43
"The critical need for iron presents a challenge for pathogenic bacteria that must survive in an environment bereft of accessible iron due to a natural low bioavailability and their host's nutritional immunity."( Diverse structural approaches to haem appropriation by pathogenic bacteria.
Hare, SA, 2017
)
0.46
"Heme is ubiquitous, yet relatively little is known about the maintenance of labile pools of this cofactor, which likely ensures its timely bioavailability for proper cellular function."( Quantification of labile heme in live malaria parasites using a genetically encoded biosensor.
Abshire, JR; Ganesan, SM; Niles, JC; Rowlands, CJ; So, PT, 2017
)
0.46
"The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans."( Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans.
Arredondo, M; Olivares, M; Pizarro, F; Valenzuela, C; Weill, R; Weinborn, V, 2017
)
0.46
" We hypothesize that the well-recognized high bioavailability of heme iron may depend on a split pathway mediating the transport of heme-derived elemental iron and intact heme from the interior of duodenal enterocytes to the bloodstream."( Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.
Bednarz, A; Gajowiak, A; Hamza, I; Korolonek, T; Krzeptowski, W; Lenartowicz, M; Lipiński, P; Pieszka, M; Smuda, E; Staroń, R; Starzyński, RR; Swinkels, DW; Van Swelm, RPL, 2017
)
0.46
" While iron is abundant in a variety of foods, its bioavailability (i."( Dietary sources of iron and vitamin B12: Is this the missing link in colorectal carcinogenesis?
Banjari, I; Hjartåker, A, 2018
)
0.48
"Irreversible aggregation can extremely limit the bioavailability and therapeutic activity of peptide-based drugs."( Heme prevents highly amyloidogenic human calcitonin (hCT) aggregation: A potential new strategy for the clinical reuse of hCT.
Gao, Z; Li, H; Ye, H; Zhou, J, 2019
)
0.51
" In order to utilize heme, while also mitigating its toxicity, cells are challenged to tightly control the concentration and bioavailability of heme."( One ring to bring them all and in the darkness bind them: The trafficking of heme without deliverers.
Chambers, IG; Hamza, I; Reddi, AR; Willoughby, MM, 2021
)
0.62
" Future research is required to estimate the iron bioavailability of Australian pre-schooler diets."( Dietary patterns of Australian pre-schoolers and associations with haem and non-haem iron intakes.
Atkins, LA; McNaughton, SA; Spence, AC; Szymlek-Gay, EA, 2021
)
0.62
" Here, we have compiled findings from preclinical and clinical studies to provide insights into the role of soluble/decoy receptors, focusing on the soluble cluster of differentiation 36, the soluble cluster of differentiation 163, and soluble lipoprotein-related protein 1 (sCD36, sCD163, and sLRP1, respectively) and the functions they could likely serve in the management of stroke, as they would notably regulate the bioavailability of the hemoglobin and heme after red blood cell lysis."( Soluble Receptors Affecting Stroke Outcomes: Potential Biomarkers and Therapeutic Tools.
Ashouri, R; Bhattacharya, A; Doré, S; Fangman, M; Garett, T; Mazur, A, 2021
)
0.62
" Although diseased blood vessels often show decreased NO bioavailability in the vascular wall, a shift of sGC heme redox balance in favor of the oxidized/apo forms can also occur."( Factors influencing the soluble guanylate cyclase heme redox state in blood vessels.
Okamura, T; Tawa, M, 2022
)
0.72
"Controlled inhibition of drug-metabolizing cytochrome P450 3A4 (CYP3A4) is utilized to boost bioavailability of anti-viral and immunosuppressant pharmaceuticals."( Interaction of CYP3A4 with Rationally Designed Ritonavir Analogues: Impact of Steric Constraints Imposed on the Heme-Ligating Group and the End-Pyridine Attachment.
Samuels, ER; Sevrioukova, IF, 2022
)
0.72
"Ritonavir is the most potent cytochrome P450 (CYP) 3A4 inhibitor in clinical use and is often applied as a booster for drugs with low oral bioavailability due to CYP3A4-mediated biotransformation, as in the treatment of HIV (e."( The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?
Beijnen, JH; Loos, NHC; Schinkel, AH, 2022
)
0.72
" CYP inducers may decrease the bioavailability and increase the clearance of drugs."( Computational Prediction of Inhibitors and Inducers of the Major Isoforms of Cytochrome P450.
Dmitriev, A; Filimonov, D; Lagunin, A; Poroikov, V; Rudik, A, 2022
)
0.72
" The 5-ALA skin permeation is considerably reduced due to its hydrophilic characteristics, decreasing its local bioavailability and therapeutic effect."( PLGA-PVA-PEG Single Emulsion Method as a Candidate for Aminolevulinic Acid (5-ALA) Encapsulation: Laboratory Scaling Up and Stability Evaluation.
Bagnato, VS; da Silva, GR; Dos Santos, AL; Dos Santos, MC; Dos Santos, SC; Inada, NM; Rodrigues de Lima, V; Sanches, EA; Soares, AC; Ţălu, Ş, 2022
)
0.72
" Conclusion: these results suggest that heme iron together with quinoa and cañihua flour could be exploited as a new safe and efficient iron supplement compared to microencapsulated iron, given its higher iron bioavailability and its ability to increase body weight."( [Effects of microencapsulated and heme iron supplementation on the recovery of hemoglobin levels in iron-depleted rats].
Choque-Quispe, M; Cossio-Bolaños, M; Donaires-Flores, T; Gómez-Campos, R; Macedo-Enriquez, E; Pacheco-Tanaka, M; Paredes-Ugarte, W; Quispe-Romero, A; Tello-Palma, E; Valencia-Pacho, M; Viza-Salas, A; Zamalloa-Cuba, W, 2022
)
0.72
" In AIP mice, preventive treatment with an experimental fusion protein of insulin and apolipoprotein A-I improved the disease by promoting fat mobilization in adipose tissue, increasing the metabolite bioavailability for the TCA cycle and inducing mitochondrial biogenesis in the liver."( Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria.
Córdoba, KM; Ena, J; Enríquez de Salamanca, R; Fontanellas, A; Jericó, D; Morales-Conejo, M; Solares, I, 2022
)
0.72
" Haem iron is obtained from animal sources such as meat and shows higher bioavailability than non-haem iron, which can be obtained from both plant and animal sources."( Factors affecting iron absorption and the role of fortification in enhancing iron levels.
Demini, SMD; Eapasinghe, DD; Faizan, M; Galhena, BP; Hays, H; Jayasinghe, JASM; Liyanage, DM; Palliyaguruge, CL; Perera, DN; Rajagopalan, U; Samarakoon, SR; Senathilake, K; Seneviratne, RACH; Tennekoon, KH, 2023
)
0.91

Dosage Studied

Heme iron intake was positively associated with the risk of upper digestive tract cancer, while zinc intake was inversely associated with risk. Pichia pastoris strain capable of high-yield secretory production of functional leghemoglobin was developed through gene dosage optimization and heme pathway consolidation.

ExcerptRelevanceReference
" At a dosage of approximately 3 mg/kg, diminution of urinary ALA and PBG excretion was achieved in every patients."( Hematin therapy for acute porphyria.
Frykholm, BC; Hess, RA; Lamon, JM; Tschudy, DP, 1979
)
0.26
" The dose-response curves obtained for both these effects closely mirror the accumulation in the liver of a compound that is labelled by 5-amino[14C]laevulinate and is unextractable by acetone/HCl."( Formation of cobalt protoporphyrin in the liver of rats. A mechanism for the inhibition of liver haem biosynthesis by inorganic cobalt.
de Matteis, F; Gibbs, AH; Sinclair, JF; Sinclair, P, 1979
)
0.26
" A method of correction for the influence of iron on the dose-response relationship of human sera is presented."( Modified method of erythropoietin (ESF) bioassay in vitro using mouse fetal liver cells. I. Effect of serum iron on 59Fe incorporation into heme.
de Klerk, G; Goudsmit, R; Hart, AA; Kruiswijk, C, 1978
)
0.26
"Red cell aplasia developed in a case of Wilson's disease following an increase in D-penicillamine dosage after 14 years' treatment."( Red cell aplasia following prolonged D-penicillamine therapy.
Gollan, JL; Hoffbrand, AV; Hussein, S; Sherlock, S, 1976
)
0.26
" Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men."( Impact of air pollution by lead on the heme biosynthetic pathway in school-age children.
Bruaux, P; Buchet, JP; Claeys-Thoreau, F; Hubermont, G; Lafontaine, A; Lauwerys, R; Roels, H; Van Overschelde, J,
)
0.13
" A final answer comes only after administration of the particular drug to man, although he is normally dosed at all events one should not overvalue the relevance of pigmentation found in long-term animal studies."( The relevance of drug-induced organ pigmentation in animals.
Pataki, A; Rentsch, G, 1976
)
0.26
" This allows a full dose-response relationship to the sera to be determined and, by a comparison with an erythropoietin standard, detailed quantitative results can be obtained."( A quantitative bioassay for erythropoietin using mouse fetal liver cells.
Dunn, CD; Greenman, JM; Jarvis, JH, 1975
)
0.25
" at the dosage of 600-1200 mg for a variable period of 3-5 days in the first group, for 7-10 days in the patients with PCT."( [Evaluation of the effects of reduced glutathione in subjects with acquired and congenital changes in heme biosynthesis].
Alessio, L; Buizza, P; De Panfilis, G; De Vincentiis, A; Ferioli, A; Leali, C; Pasolini, G, 1992
)
0.28
"The influence of multiple sublethal concentrations of phosalone on whole animal and kidney oxygen consumption, haem synthesis and blood gases of rat, were carried out over a 90 day dosed period."( Effect of chronic insecticide, phosalone, toxicity on haem synthesis and blood gas composition in the rat.
Ramamurthi, R; Reddy, BV; Reddy, SJ, 1992
)
0.28
"7 h of the dosing interval with a wide degree of variability."( Pharmacokinetics of ranitidine in critically ill infants.
Brundage, RC; Gillette, PC; O'Neal, W; Reigart, JR; Wiest, DB; Yost, RL, 1989
)
0.28
" In the liver of the DL-buthionine-(S,R)-sulfoximine (BSO)-treated rats dosed with m-DCB, both of 2,4- and 3,5-DCPSO2Mes were present at significantly lower concentrations than in non-BSO-treated rats."( Contribution of methylsulfonyl metabolites of m-dichlorobenzene to the heme metabolic enzyme induction by the parent compound in rat liver.
Kato, Y; Kimura, R; Kogure, T; Sato, M, 1988
)
0.27
" The severe impairment of hepatic mixed function oxidase activity even in the symptomless stage of porphyria indicates cautious dosage of drugs primarily eliminated by hepatic oxidative reactions."( Haem arginate improves hepatic oxidative metabolism in variegate porphyria.
Himberg, JJ; Mustajoki, P; Tokola, O, 1988
)
0.27
" The sulfide dosing caused decreased activity of both enzymes of which that of heme synthase was overcorrected above controls by the heme treatment 25 h after the sulfide dose."( Effect of exogenous heme on sulfide-induced changes in rat heme metabolism.
Savolainen, H; Tenhunen, R, 1987
)
0.27
" The results demonstrate that the dose-response relationships for hepatic induction and lethality are dissociated and that the maximal induction levels are not correlated with the incidence of lethality."( Polychlorinated aromatic hydrocarbon lethality, mixed-function oxidase induction, and uroporphyrinogen decarboxylase inhibition in the chick embryo: dissociation of dose-response relationships.
Muschick, H; Reyes, J; Rifkind, AB; Sassa, S, 1985
)
0.27
" Within this time interval, hepatic heme oxygenase (HO) activity increased and at 8 hr after dosing was 7-fold greater than control values in the livers, but was unchanged in the kidneys and spleens of DDTC-treated animals."( Mechanisms of diethyldithiocarbamate-induced loss of cytochrome P-450 from rat liver.
Greene, FE; Miller, GE; Zemaitis, MA, 1983
)
0.27
" In any case, the dosage of both parenteral and oral therapy will have to be adjusted individually."( [Successful treatment of acne with Actovegin].
Bias, K, 1980
)
0.26
" Secondly, the fact that the pattern of absorption in relation to dosage was so different for haem iron and non-haem iron suggested that a controlling mechanism for non-haem iron absorption may be located at the mucosal surface."( The relative dietary importance of haem and non-haem iron.
Bezwoda, WR; Bothwell, TH; Charlton, RW; Derman, DP; MacPhail, AP; Mayet, F; Torrance, JD, 1983
)
0.27
"We have determined the dose-response curves (100-900 mg of Fe/kg body wt."( Iron and the liver. Acute and long-term effects of iron-loading on hepatic haem metabolism.
Bonkowsky, HL; Healey, JF; Pomeroy, JS; Sinclair, JF; Sinclair, PR, 1981
)
0.26
" A sigmoidal dose-response curve is followed with 50% hemolysis being produced by 4 microM FP."( Hemolysis of mouse erythrocytes by ferriprotoporphyrin IX and chloroquine. Chemotherapeutic implications.
Chou, AC; Fitch, CD, 1980
)
0.26
" Dose-response studies showed that SA (250 microM) did not affect cell viability or growth up to 72 h, but resulted in inhibition of ALA-D activity (> 93%) and decreased cellular levels of both heme and MPO (approximately 25% of control)."( The post-translational processing of myeloperoxidase is regulated by the availability of heme.
Bonkovsky, HL; Guzman, GS; Kinkade, JM; Pinnix, IB; Zaki, SR, 1994
)
0.29
" Genetic manipulations involved amplifying the gene dosage for the enzymes ALA synthase and ALA dehydratase."( Effect of biosynthetic manipulation of heme on insolubility of Vitreoscilla hemoglobin in Escherichia coli.
Bailey, JE; Hart, RA; Kallio, PT, 1994
)
0.29
" Dose-response data indicated that only nanomolar concentrations of zinc mesoporphyrin and heme are required to obtain this effect."( Repression of hepatic delta-aminolevulinate synthase by heme and metalloporphyrins: relationship to inhibition of heme oxygenase.
Bonkovsky, HL; Cable, EE; Cable, JW, 1993
)
0.29
" This review highlights some of the challenges faced by pharmaceutical scientists in formulating these drugs into stable, effective, and safe dosage forms."( Pharmaceutics and drug delivery aspects of heme and porphyrin therapy.
Cannon, JB, 1993
)
0.29
"The effect of recombinant human interleukin-1beta (IL-1beta) on the modulation of hepatic cytochrome P450 (P450) was investigated by in vivo subcutaneous dosing studies in male Sprague-Dawley rats."( Role of interleukin-1beta in the modulations of cytochrome P450 and heme metabolism in rat liver.
Kawano, K; Kudo, S, 1999
)
0.3
" The therapeutic dosage of HU used for Hb F induction often elicits myelosuppression, which becomes its major associated complication."( Hydroxyurea-induced oxidative damage of normal and sickle cell hemoglobins in vitro: amelioration by radical scavengers.
Asakura, T; del Pilar Aguinaga , M; Fasold, H; Iyamu, EW; Roa, D; Turner, EA, 2001
)
0.31
" Through the use of iron isotopes ((59)Fe and (55)Fe), the studies were performed to characterize the dose-response curve of non-heme-iron absorption (ferrous sulfate), and to establish the dose-response curve of heme-iron absorption (hemoglobin)."( Heme-iron absorption is saturable by heme-iron dose in women.
Arredondo, M; Hertrampf, E; Mazariegos, DI; Olivares, M; Pizarro, F, 2003
)
0.32
" We also found that Hap1 activity exhibits the same oxygen dose-response curves as Hap1-dependent aerobic genes and that these dose-response curves have a sharp break at approximately 1 microM O2."( A mechanism of oxygen sensing in yeast. Multiple oxygen-responsive steps in the heme biosynthetic pathway affect Hap1 activity.
Dirmeier, R; Dodd, A; Gorman, N; Hon, T; Poyton, RO; Sinclair, PR; Zhang, L, 2003
)
0.32
" This study was designed to determine whether enterally dosed recombinant Epo (rEpo) stimulates erythropoiesis in preterm neonates."( Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates.
Juul, SE, 2003
)
0.32
"Enterally dosed rEpo (1000 U/kg/day) does not significantly influence erythropoiesis or iron utilization when given for a 2-week period, nor does it elevate the serum Epo concentration in preterm or term infants."( Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates.
Juul, SE, 2003
)
0.32
" Dose-response studies identified the residues most prone to oxidation to be Phe-36, Phe-46, and Met-80."( Hydroxyl radical oxidation of cytochrome c by aerobic radiolysis.
Anderson, VE; Nukuna, BN; Sun, G, 2004
)
0.32
" When heme iron and zinc were mutually adjusted, in dose-response manners, heme iron intake was positively associated with the risk of upper digestive tract cancer, while zinc intake was inversely associated with risk."( Heme iron, zinc and upper digestive tract cancer: the Iowa Women's Health Study.
Anderson, KE; Folsom, AR; Jacobs, DR; Lee, DH, 2005
)
0.33
" Channel catfish (Ictalurus punctatus) were dosed with mixtures of benzo[a]pyrene and cadmium, chlorinated phenols or borneol."( Heme oxygenase induction and biliverdin excretion: implications for the bile fluorescence biomarker.
van den Hurk, P, 2006
)
0.33
"0 in dosage of 15-20 drops per minute was applied."( [Assessment of fetus' hypoxia treatment with actovegin].
Lominadze, AA; Sharvashidze, NK, 2006
)
0.33
" The lack of translocation of DMT1 with heme dosing suggests another protein may be present to transport iron released from heme."( Subcellular location of heme oxygenase 1 and 2 and divalent metal transporter 1 in relation to endocytotic markers during heme iron absorption.
Oates, PS; West, AR, 2008
)
0.35
" Aktovegin has been used in drops in dosage 400 mg per 200 ml physiological solution for 10 days."( [Actovegin in the treatment of brain injuries of mild and moderate severity].
Ioffe, IuS; Kuksova, NS; Miatchin, MIu; Talypov, AE, 2008
)
0.35
" Ceraxon in daily dosage 2 g and cerebrolysin in daily dosage 10 ml during 10 days after the development of ischemic stroke led to the significantly better regression of neurological symptoms to the 21st day of disease compared to the control group."( [Comparative aspects of using neuroprotectors in the management of patients with ischemic stroke].
Ershov, VI, 2011
)
0.37
" When iron stores are not replete at the end of treatment, compliance and dosage must be reevaluated and occult bleeding sought."( [Diagnosis of hypochromic microcytic anemia in children].
Beaumont, C; Bresson, JL; Brouzes, C; de Montalembert, M; Puy, H; Ruemmele, FM, 2012
)
0.38
" HO-1 competitive inhibitor zinc protoporphyrin improved the cytotoxicity of arsenic in an inverted-U dose-response curve, indicating the biphasic hormetic effect of HO-1."( Arsenic modulates heme oxygenase-1, interleukin-6, and vascular endothelial growth factor expression in endothelial cells: roles of ROS, NF-κB, and MAPK pathways.
Hu, LW; Kou, MC; Wang, L; Wang, YJ; Weng, CY; Wu, MJ, 2012
)
0.38
"This meta-analysis suggests a significant positive dose-response association of heme iron intake and a significant inverse dose-response association of zinc intake with risk of CRC."( Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies.
Feng, Y; Qiao, L, 2013
)
0.39
" The participant numbers with impaired glucose tolerance and impaired fasting glucose decreased in the highest dosage group of ALA-P plus iron compared with the placebo group."( 5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects.
Awaya, T; Higashikawa, F; Noda, M; Sugiyama, M; Tanaka, T,
)
0.13
"2 years) received actovegin intramuscularly in dosage 5 ml (200 mg) daily during 4 weeks."( [Efficacy of actovegin in the treatment of elderly patients with vascular mild cognitive impairment].
Gavrilova, SI; Kalyn, IaB; Mikhaĭlova, NM; Roshchina, IF; Selezneva, ND, 2013
)
0.39
"62 g volatile suspended solid (VSS) sludges were varied to optimize bio-augmentation dosage (BAD), and appropriate bio-augmentation time (BAT) was determined."( Bio-augmentation for mitigating the impact of transient oxytetracycline shock on anaerobic ammonium oxidation (ANAMMOX) performance.
Guo, LX; Jin, RC; Liu, JH; Wang, HZ; Yang, BE; Zhang, QQ; Zhang, ZZ, 2014
)
0.4
" This meta-analysis was performed to investigate the dose-response association between dietary intake of iron (including heme and non-heme iron) and the risk of CVD."( Dietary intake of heme iron and risk of cardiovascular disease: a dose-response meta-analysis of prospective cohort studies.
An, P; Fang, X; Li, X; Liu, S; Min, J; Shen, X; Wang, F; Wang, H; Wang, X, 2015
)
0.42
" Because of many of the above factors, especially CYP polymorphisms, there has been much interest in personalized medicine especially with respect to which CYPs and which of their polymorphic forms are present in order to attempt to determine what drug therapy and what dosage would reflect the best therapeutic strategy in treating individual patients."( Molecular mechanisms of the microsomal mixed function oxidases and biological and pathological implications.
Cederbaum, AI, 2015
)
0.42
" Future studies should pay attention to the delicate balance between sufficient dosing and timely normalization of plasma haem levels."( Vascular and metabolic effects of the haem oxygenase-1 inducer haem arginate in subjects with the metabolic syndrome: A translational cross-over study.
Bilos, A; Dekker, D; Dorresteijn, MJ; Pennings, SW; Peters, WH; Smits, P; Wagener, FA, 2016
)
0.43
" Additionally, meta-regression analyses and stratified intake analyses were conducted to evaluate dose-response relationships."( A review and meta-analysis of prospective studies of red and processed meat, meat cooking methods, heme iron, heterocyclic amines and prostate cancer.
Alexander, DD; Bylsma, LC, 2015
)
0.42
"As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12."( Improved safety margin for embryotoxicity in rats for the new endoperoxide artefenomel (OZ439) as compared to artesunate.
Andenmatten, N; Clark, RL; Clode, SA; Edwards, TL; Huber, AC; Kinney, J; Longo, M; Rhodes, J; Rückle, T; Walker, DK; Wells, T, 2018
)
0.48
" Investigation of pyrazoles, especially N-alkyl pyrazoles, as a new template to coordinate the heme-iron motif led to a potent and highly selective CYP11B2 inhibitor 28 with an aldosterone-lowering effect at 1 mg/kg dosing in cynomolgus monkeys."( Discovery of Novel Pyrazole-Based Selective Aldosterone Synthase (CYP11B2) Inhibitors: A New Template to Coordinate the Heme-Iron Motif of CYP11B2.
Akahoshi, F; Egi, Y; Hiraga, Y; Nishio, M; Ohbora, T; Onda, Y; Sakakibara, R; Sasaki, W; Sato, K; Shimizu, H; Takedomi, K; Ushirogochi, H; Yamaguchi, M, 2018
)
0.48
" Repeat dosing in AIP mice showed sustained efficacy and therapeutic improvement without evidence of hepatotoxicity."( Systemic messenger RNA as an etiological treatment for acute intermittent porphyria.
Alegre, M; Ávila, MA; Benenato, KE; Berraondo, P; Burke, K; Butcher, W; Fontanellas, A; Frassetto, A; Guey, LT; Jericó, D; Jiang, L; Kalariya, M; Kenney, M; Kumarasinghe, ES; Lukacs, CM; Martini, PGV; Park, JS; Pejenaute, Á; Sabnis, S; Salerno, T; Sampedro, A; Santamaría, E; Zhu, X, 2018
)
0.48
" Results- Low dosage imiquimod significantly attenuated hematoma volume, brain edema, BBB permeability, and neurological deficits after ICH."( TLR7 (Toll-Like Receptor 7) Facilitates Heme Scavenging Through the BTK (Bruton Tyrosine Kinase)-CRT (Calreticulin)-LRP1 (Low-Density Lipoprotein Receptor-Related Protein-1)-Hx (Hemopexin) Pathway in Murine Intracerebral Hemorrhage.
Budbazar, E; Guo, Z; Krafft, PR; Tang, J; Tong, L; Wang, G; Xue, F; Zhang, JH, 2018
)
0.48
" Depending on the dosage all patients were divided in two groups: Actovegin 1000 mg and 160 mg daily."( Multimodal approach to treatment of neurological complications of chronic brain ischemia.
Konovalov, RN; Lagoda, OV; Raskurazhev, AA; Shabalina, AA; Tanashyan, MM, 2018
)
0.48
" Dose-response meta-analyses were also performed to investigate linear and nonlinear associations."( Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis.
Chang, VC; Cotterchio, M; Khoo, E, 2019
)
0.51
"This quantitative framework provides a valuable tool to compare PBGD mRNA drug products during early preclinical stages, optimize the amount of experimental data required, and project results to humans, thus supporting drug development and clinical dose and dosing regimen selection."( Disease pharmacokinetic-pharmacodynamic modelling in acute intermittent porphyria to support the development of mRNA-based therapies.
Fontanellas, A; Guey, LT; Hard, M; Jericó, D; Jiang, L; Martini, P; Parra-Guillen, ZP; Troconiz, IF; Vera-Yunca, D, 2020
)
0.56
"Heme iron possesses powerful carcinogenic and anticarcinogenic properties which are dosage and oxygen availability dependant."( Dual role of heme iron in cancer; promotor of carcinogenesis and an inducer of tumour suppression.
Dissabandara, DLO; Gamage, SMK; Gopalan, V; Lam, AK; Lee, KTW, 2021
)
0.62
" The sustained efficacy of givosiran in most patients allowed us to personalize dosing frequency."( Givosiran in acute intermittent porphyria: A personalized medicine approach.
Bouchoule, I; Cerutti, D; Douillard, C; Duchêne, F; Dupré, T; Faivre, A; Fiorentino, V; Gouya, L; Grobost, V; Lefebvre, T; Manceau, H; Mirmiran, A; Moulouel, B; Peoc'h, K; Poli, A; Puy, H; Rivière, S; Schmitt, C; Talbi, N, 2022
)
0.72
"The sustained effect of givosiran allowed a decrease in dosing frequency without compromising treatment efficacy."( Givosiran in acute intermittent porphyria: A personalized medicine approach.
Bouchoule, I; Cerutti, D; Douillard, C; Duchêne, F; Dupré, T; Faivre, A; Fiorentino, V; Gouya, L; Grobost, V; Lefebvre, T; Manceau, H; Mirmiran, A; Moulouel, B; Peoc'h, K; Poli, A; Puy, H; Rivière, S; Schmitt, C; Talbi, N, 2022
)
0.72
" Dose-response associations were modeled by a one-stage weighted mixed-effects meta-analysis."( Dietary iron intake and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective cohort studies.
Jayedi, A; Shab-Bidar, S; Shahinfar, H, 2022
)
0.72
" However, increase in pehA dosage enhanced colonization fitness about 30 fold in the root and 900 fold in the root apex."( Improvement of fitness and biocontrol properties of Pseudomonas putida via an extracellular heme peroxidase.
De Bruyne, L; Höfte, M; Ramos-González, MI; Santamaría-Hernando, S, 2022
)
0.72
" Here, a Pichia pastoris strain capable of high-yield secretory production of functional leghemoglobin was developed through gene dosage optimization and heme pathway consolidation."( High-level secretory production of leghemoglobin in Pichia pastoris through enhanced globin expression and heme biosynthesis.
Huang, L; Lian, J; Liu, W; Shao, Y; Wei, P; Xu, Z; Xue, C; Zuo, S, 2022
)
0.72
" We utilized a randomized, crossover, open (blinded laboratory) and placebo-controlled trial with 600-mg rifampicin or placebo dosed for a week to investigate the effects of PXR activation on erythrocyte, plasma, faecal and urine porphyrins."( Effects of rifampicin on porphyrin metabolism in healthy volunteers.
Hämäläinen, E; Hukkanen, J; Kauppinen, R; Ranta, S; Tolonen, H, 2023
)
0.91
" Dose-response analyses further revealed a U-shaped association of total and nonheme iron intake and an L-shaped association of heme iron intake with hypertension risk in both men and women (all P for non-linearity < 0."( Dietary intakes of total, nonheme, and heme iron and hypertension risk: a longitudinal study from the China Health and Nutrition Survey.
Chen, P; Fang, A; He, J; Li, K; Liu, Z; Sui, Y; Wu, S, 2023
)
0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Pathways (119)

PathwayProteinsCompounds
Transport of small molecules39295
ABC-family proteins mediated transport7711
Mitochondrial ABC transporters46
Iron uptake and transport2919
O2/CO2 exchange in erythrocytes811
Erythrocytes take up carbon dioxide and release oxygen811
Erythrocytes take up oxygen and release carbon dioxide88
Intracellular oxygen transport32
Metabolism14961108
Metabolism of nitric oxide: NOS3 activation and regulation1426
eNOS activation and regulation1326
eNOS activation1026
NOSIP mediated eNOS trafficking25
NOSTRIN mediated eNOS trafficking54
Metabolism of vitamins and cofactors146155
Metabolism of water-soluble vitamins and cofactors102114
Vitamin C (ascorbate) metabolism418
Metabolism of cofactors1947
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation1025
Amino acid and derivative metabolism250260
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism4485
Tryptophan catabolism1426
Sulfur amino acid metabolism2763
Cysteine formation from homocysteine28
Selenoamino acid metabolism2450
Metabolism of ingested SeMet, Sec, MeSec into H2Se423
Porphyrin metabolism2344
Heme biosynthesis1530
Heme degradation1021
Signaling Pathways1269117
Signaling by Receptor Tyrosine Kinases29335
Signaling by VEGF6225
VEGFA-VEGFR2 Pathway5225
VEGFR2 mediated vascular permeability2016
Signaling by Rho GTPases18120
RHO GTPase Effectors16620
RHO GTPases Activate NADPH Oxidases1812
Cellular responses to stimuli48356
Cellular responses to stress46954
Detoxification of Reactive Oxygen Species3027
Disease1278231
Infectious disease89579
Latent infection of Homo sapiens with Mycobacterium tuberculosis3232
Latent infection - Other responses of Mtb to phagocytosis3233
Tolerance by Mtb to nitric oxide produced by macrophages1121
Tolerance of reactive oxygen produced by macrophages118
Mtb iron assimilation by chelation610
heme a biosynthesis07
superpathway of proto- and siroheme biosynthesis1638
Immune System91482
Innate Immune System41475
ROS and RNS production in phagocytes1237
heme b biosynthesis I (aerobic)612
superpathay of heme b biosynthesis from glutamate1128
Infection with Mycobacterium tuberculosis7442
phytochromobilin biosynthesis17
heme degradation I014
SARS-CoV Infections28229
SARS-CoV-2 Infection19527
Heme signaling307
Cellular response to chemical stress16740
Cytoprotection by HMOX13419
Signaling by Rho GTPases, Miro GTPases and RHOBTB318520
Antiviral and anti-inflammatory effects of Nrf2 on SARS-CoV-2 pathway16
SARS-CoV-2-host interactions1559
SARS-CoV-2 targets host intracellular signalling and regulatory pathways123
superpathway of heme b biosynthesis from glutamate022
cytochrome c biogenesis (system III type)01
Bacterial Infection Pathways12347
Viral Infection Pathways72739
NAD de novo biosynthesis1233
heme biosynthesis from uroporphyrinogen-III I413
heme biosynthesis920
tryptophan degradation1345
L-kynurenine degradation1352
superpathway of tryptophan utilization4292
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde722
nitrate reduction III (dissimilatory)1219
hydrogen to trimethylamine N-oxide electron transfer916
formate to nitrite electron transfer714
heme b biosynthesis III (from siroheme)113
heme b biosynthesis II (anaerobic)413
heme b biosynthesis IV (Gram-positive bacteria)314
superpathay of heme b biosynthesis from glutamate2047
superpathway of heme b biosynthesis from uroporphyrinogen-III517
superpathway of b heme biosynthesis from glycine1046
heme b biosynthesis I (aerobic)1428
succinate to cytochrome bo oxidase electron transfer831
NADH to cytochrome bd oxidase electron transfer II418
NADH to cytochrome bo oxidase electron transfer II526
D-lactate to cytochrome bo oxidase electron transfer527
glycerol-3-phosphate to cytochrome bo oxidase electron transfer529
proline to cytochrome bo oxidase electron transfer531
succinate to cytochrome bd oxidase electron transfer723
NADH to cytochrome bo oxidase electron transfer I1734
NADH to cytochrome bd oxidase electron transfer I1627
pyruvate to cytochrome bo oxidase electron transfer535
heme degradation V213
heme degradation IV18
heme degradation VI28
heme degradation III19
heme degradation VII18
heme degradation II38
heme degradation I314
phycoerythrobilin biosynthesis II09
phycoviolobilin biosynthesis49
phycoerythrobilin biosynthesis I310
phycourobilin biosynthesis410
phytochromobilin biosynthesis49
phycocyanobilin biosynthesis59
heme a biosynthesis410
superoxide radicals degradation914
trans-lycopene biosynthesis II (oxygenic phototrophs and green sulfur bacteria)814
formate to trimethylamine N-oxide electron transfer815
hydrogen to dimethyl sulfoxide electron transfer1015
formate to dimethyl sulfoxide electron transfer914
superpathway of heme biosynthesis818
heme biosynthesis from uroporphyrinogen-III II012
citrulline-nitric oxide cycle523
heme biosynthesis III (from siroheme)110
Folic acid network070
Iron uptake and transport030
Selenium micronutrient network095
Folate metabolism156
Biochemical pathways: part I0466
Heme synthesis324

Research

Studies (18,581)

TimeframeStudies, This Drug (%)All Drugs %
pre-19906216 (33.45)18.7374
1990's2859 (15.39)18.2507
2000's4295 (23.12)29.6817
2010's3885 (20.91)24.3611
2020's1326 (7.14)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials115 (0.60%)5.53%
Reviews1,877 (9.83%)6.00%
Case Studies181 (0.95%)4.05%
Observational12 (0.06%)0.25%
Other16,901 (88.55%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]