Photomedicine based on heme-derived compounds.

Photoimaging and phototherapy have become major platforms for the diagnosis and treatment of various health complications. These applications require a photosensitizer (PS) that is capable of absorbing light from a source and converting it into other energy forms for detection and therapy. While synthetic inorganic materials such as quantum dots and gold nanorods have been widely explored for their medical diagnosis and photodynamic (PDT) and photothermal (PTT) therapy capabilities, translation of these technologies has lagged, primarily owing to potential cytotoxicity and immunogenicity issues. Of the various photoreactive molecules, the naturally occurring endogenous compound heme, a constituent of red blood cells, and its derivatives, porphyrin, biliverdin and bilirubin, have shown immense potential as noteworthy candidates for clinically translatable photoreactive agents, as evidenced by previous reports. While porphyrin-based photomedicines have attracted significant attention and are well documented, research on photomedicines based on two other heme-derived compounds, biliverdin and bilirubin, has been relatively lacking. In this review, we summarize the unique photoproperties of heme-derived compounds and outline recent efforts to use them in biomedical imaging and phototherapy applications.

Intramuscular Injection of Combined Calf Blood Compound (CFC) and Homeopathic Drug Tr14 Accelerates Muscle Regeneration In Vivo.

Skeletal muscle injuries in competitive sports cause lengthy absences of athletes from tournaments. This is of tremendous competitive and economic relevance for both the athletes and their respective clubs. Therapy for structural muscle lesions aims to promote regeneration and fast-track return-to-play. A common clinical treatment strategy for muscle injuries is the intramuscular injection of calf blood compound and the homeopathic drug, Tr14. Although the combination of these two agents was reported to reduce recovery time, the regulatory mechanism whereby this occurs remains unknown. In this in vivo study, we selected a rat model of mechanical muscle injury to investigate the effect of this combination therapy on muscle regeneration. Gene expression analysis and histological images revealed that this combined intramuscular injection for muscle lesions can enhance the expression of pro-myogenic genes and proteins and accelerate muscle regeneration. These findings are novel and depict the positive effects of calf blood compound and the homeopathic drug, Tr14, which are utilized in the field of Sports medicine.

Dietary intake of heme iron and body iron status are associated with the risk of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Some potential role of iron overload in the development of diabetes mellitus have been suggested. Our study aimed to systematically assess the association between the risk of gestational diabetes mellitus (GDM) and iron intakes/body iron status. METHODS AND STUDY DESIGN: PubMed and Web of Science were searched for relevant articles. Relative risks (RR) of GDM in relation to dietary iron intakes and body iron stores were pooled with the random-effects model. Weighted mean differences of iron blood markers between GDM and non-GDM individuals were also analyzed. RESULTS: Twenty-five studies were included in the qualitative analysis, and 23 studies with 29,378 participants and 3,034 GDM patients were included in the quantitative analysis. Dietary intake of heme iron was significantly associated with GDM risk (RR=1.65, 95% CI: 1.28 to 2.12), and the pooled RR for each 1mg/day increment of heme iron intake was 1.38 (95% CI: 1.19 to 1.61). No association between GDM and the intakes of nonheme iron, total iron, or supplemental iron was detected. Body iron stores, as represented by serum ferritin level, were correlated with GDM risk (RR=1.64, 95% CI: 1.27 to 2.11). Moreover, the concentrations of both serum ferritin and serum iron were increased in GDM patients, compared with non-GDM individuals. CONCLUSIONS: Increased dietary intake of heme iron and body iron status are positively associated with the risk of GDM development in pregnant women. Future studies are warranted to better understand the role of iron in GDM development.

Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.

Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status. Our results revealed a concerted increase in the expression of genes responsible for apical and basolateral heme transport in the duodenum of piglets fed a heme-enriched diet. In these animals the catalytic activity of heme oxygenase 1 contributed to the release of elemental iron from the protoporphyrin ring of heme within enterocytes, which may then be transported by the strongly expressed ferroportin across the basolateral membrane to the circulation. 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.

Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet.

Double enzymatic hydrolysis preparation of heme from goose blood and microencapsulation to promote its stability and absorption.

Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide. This deficiency could be solved by preparing stable, edible, and absorbable iron food ingredients using environmentally friendly methods. This study investigated enzymatic hydrolysis and microencapsulation process of goose blood. The physicochemical properties, stabilities of the microencapsulated goose blood hydrolysate (MGBH) and a supplement for rats with IDA were also evaluated. The results showed that the synergetic hydrolytic action of neutrase and alkaline protease significantly increased the heme-releasing efficiency. The heme was then microencapsulated using sodium caseinate, maltodextrin and carboxymethyl cellulose (CMC) as the edible wall material, and the encapsulation efficiency of the product reached 98.64%. Meanwhile, favorable thermal, storage and light stabilities were observed for the microencapsulation. It was found that MGBH can significantly improve the body weight and hematological parameters of IDA Wistar rat.

Dietary intake of heme iron and risk of cardiovascular disease: a dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND AIMS: Iron is thought to play a fundamentally important role in the development of cardiovascular disease (CVD). 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. METHODS AND RESULTS: We performed a search of the PubMed and Embase databases for prospective cohort studies of the association between dietary iron intake and CVD risk. Thirteen articles comprising 252,164 participants and 15,040 CVD cases were eligible for inclusion. Heme iron intake was associated significantly with increased risk of cardiovascular disease, and the pooled relative risk (RR) for each 1 mg/day increment was 1.07 (95% confidence interval: 1.01 to 1.14, I² = 59.7%). We also found evidence of a curvilinear association (P < 0.05 for non-linearity). In contrast, we found no association between CVD risk and dietary non-heme (0.98, 0.96 to 1.01, I² = 15.8%) or total iron (1.00, 0.94 to 1.06, I² = 30.4%). Subgroup analyses revealed that the association between heme iron intake and CVD risk was stronger among non-fatal cases (1.19, 1.07-1.33) and American patients (1.31, 1.11-1.56). CONCLUSIONS: Higher dietary intake of heme iron is associated with an increased risk of cardiovascular disease, whereas no association was found between CVD and non-heme iron intake or total iron intake. These findings may have important public health implications with respect to preventing cardiovascular disease.

Myotoxicity of injections for acute muscle injuries: a systematic review.

BACKGROUND: Injection therapies are widely used for muscle injuries. As there is only limited evidence of their efficacy, physicians should be aware of the potential harmful effects of these injected preparations. OBJECTIVES: The purpose of this review was to systematically review the literature on the myotoxic effects of intramuscular injection preparations commonly used for acute muscle injuries. DATA SOURCES: The databases of PubMed, Embase, Web of Science, Cochrane Library, CINAHL and SportDiscus were searched in March 2013. STUDY ELIGIBILITY CRITERIA: Studies reporting histological evaluation or creatine kinase activity after intramuscular injection with local anaesthetics, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), platelet-rich plasma (PRP), Traumeel(®) and Actovegin(®), or combination preparations were eligible for inclusion. DATA ANALYSIS: Two authors independently screened the search results and assessed the risk of bias. A best-evidence synthesis was used to identify the level of evidence. RESULTS: Forty-nine studies were included in this systematic review. There is strong to moderate evidence that intramuscularly injected local anaesthetics and NSAIDs are myotoxic, and there is conflicting evidence of the myotoxicity of PRP. There is limited evidence that single corticosteroid injections are not myotoxic but have a synergistic myotoxic effect when used together with local anaesthetics. There is no information to assess whether Actovegin(®) and Traumeel(®) are myotoxic. CONCLUSION: Local anaesthetics and NSAID injections are not recommended for the treatment of muscle injuries in athletes, as they are myotoxic. The possible myotoxic effects of corticosteroids, PRP, Traumeel(®) and Actovegin(®) should be assessed in future research.

Effects of heme iron enriched peptide on iron deficiency anemia in rats.

The present study aims to investigate whether a daily intake of heme iron enriched peptide obtained from bovine hemoglobin is effective in alleviating iron deficiency anemia (IDA). Wistar rats were randomly divided into six groups: a control group, an anemic group not treated, and anemic groups treated with FeSO4 or with the heme iron enriched peptide at low, moderate or high doses. The rats in the anemic groups were fed on a low-iron diet to establish the iron deficiency anemia model. After the model had been established, different doses of heme iron enriched peptide were given to the rats once a day via intragastric administration. After the iron supplement administration, it was observed that heme iron enriched peptide had effective restorative action returning the hemoglobin, red blood cells, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration and serum iron in IDA animals to normal values or better. In addition, compared with FeSO4, higher Fe bioavailability and fewer side effects were observed. The rats in the moderate dose group had the highest apparent Fe absorption. Moreover, in vivo antioxidant activity was also observed, enhancing the activities of antioxidant enzymes and reduced malondialdehyde levels in IDA rats. Furthermore, the heme iron enriched peptide also exhibited strong in vitro antioxidant activities. In conclusion, heme iron enriched peptide significantly alleviated iron deficiency anemia, and exhibited strong in vitro and in vivo antioxidant activities. This suggests that heme iron enriched peptide might be exploited as a safe, efficient new iron supplement.

Effect of iron liposomes on anemia of inflammation.

Supplementation with iron-fortified foods is an effective method for treating iron deficiency diseases. However, traditional iron agents used to treat anemia of inflammation (AI) have little effect. In this study, two types of iron liposomes, heme liposomes (HEME-LIP) and ferric citrate liposomes (FAC-LIP), were prepared by the rotary-evaporated film-ultrasonication method, and the encapsulation efficiencies, microstructures, size distributions and zeta potentials were assessed. Both types of iron liposomes showed stable physical characteristics. When used to treat rat models of AI, FAC-LIP and HEME-LIP could increase serum iron levels by 119% and 54% higher than did ferric citrate (FAC) and heme, respectively. Furthermore, the hepcidin, a key regulator of iron homeostasis was up-regulated by these iron liposomes, especially by HEME-LIP. These results indicate that the absorption of iron liposomes was improved over that of unencapsulated iron agents. Thus, iron liposomes may be used to fortify food in treating iron deficiency diseases, especially AI.

[Dietary supplement of iron for iron deficiency]. / Kosttilskudd med jern ved jernmangel.

BACKGROUND: A low supply of iron in the diet may result in iron deficiency and mild iron-deficiency anaemia in healthy individuals. Women are more susceptible than men because of menstrual iron loss. We compared the effect of a low dose of iron, administered as a dietary supplement, with a high pharmacological dose of iron to otherwise healthy individuals with iron deficiency and mild iron deficiency anaemia. MATERIAL AND METHOD: In a randomised, double-blind trial conducted in 2000-2001, 73 women and three men with iron deficiency received either 27.6 mg of iron consisting of ferrous fumarate enriched with 13% haem iron, or 100 mg ferrosulphate daily for 12 weeks. Blood samples were analysed four times in the course of the treatment. RESULTS: The median ferritin value rose by 13 and 7 µg/l in the high-dose and low-dose group, respectively. The increase in ferritin was significantly higher in the high-dose than in the low dose group ( < 0.001). There was no statistically significant difference between the groups in the change in Hb, serum-iron or serum-iron binding capacity. The median haemoglobin value increased by 0.4 g/100 ml in both groups. Gastrointestinal side effects were experienced by 58% in the high-dose group and 35% in the low-dose group. Four subjects in the high-dose group and one in the low-dose group broke off the treatment because of side effects. INTERPRETATION: A supplement of low-dose iron is enough to increase iron stores in cases of nutritional iron deficiency in healthy individuals and to optimise haemoglobin. High-dose iron caused the largest increase in iron stores. Low-dose iron resulted in the least side effects.

Dietary heme induces acute oxidative stress, but delayed cytotoxicity and compensatory hyperproliferation in mouse colon.

Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by generating cytotoxic and oxidative stress. Recently, we found that this surface injury is compensated by hyperproliferation and hyperplasia of crypt cells, which was induced by a changed surface to crypt signaling. It is unknown whether this changed signaling is caused by cytotoxic stress and/or oxidative stress, as these processes were never studied separately. The aim of this study was to determine the possible differential effects of dietary heme on these luminal stressors and their impact on the colonic mucosa after 2, 4, 7 and 14 days of heme feeding. Mice received a purified, humanized, control diet or the diet supplemented with 0.2 µmol heme/g. Oxidative and cytotoxic stress were measured in fecal water. Proliferation was determined by Ki67-immunohistochemistry and mucosal responses by whole-genome transcriptomics. After heme ingestion, there was an acute increase in reactive oxygen species (ROS) leading to increased levels of lipid peroxidation products. Mucosal gene expression showed an acute antioxidant response, but no change in cell turnover. After day 4, cytotoxicity of the colonic contents was increased and this coincided with differential signaling and hyperproliferation, indicating that cytotoxicity was the causal factor. Simultaneously, several oncogenes were activated, whereas the tumor suppressor p53 was inhibited. In conclusion, luminal cytotoxicity, but not ROS, caused differential surface to crypt signaling resulting in mucosal hyperproliferation and the differential expression of oncogenes and tumor suppressor genes.

Heme iron-based dietary intervention for improvement of iron status in young women.

OBJECTIVE: Conventional iron deficiency treatment with pharmacologic iron doses often causes side effects. Heme iron has high bioavailability and a low capacity to cause gastrointestinal side effects. This study investigated the possibility of using heme iron in the form of blood-based crisp bread as a diet-based treatment program to improve the iron status of women of reproductive age. METHODS: In a 12-wk intervention study, 77 women (mean age 24 y) were assigned to one of four groups: blood-based crisp bread (35 mg of iron [Fe], 27 mg of which was heme Fe), iron supplementation consisting of 35 mg of non-heme iron/day (Fe35), iron supplementation consisting of 60 mg of non-heme iron/day (Fe60), and controls (iron-free tablets). RESULTS: Body iron increased significantly in the crisp bread group by a median of 2.7 mg/kg (interquartile range 3.1, n = 18), in the Fe35 group by 2.7 mg/kg (interquartile range 2.8, n = 11), and in the Fe60 group by 4.1 mg/kg (interquartile range 3.6, n = 13), whereas no change was observed in the control group. No statistically significant difference in iron status increase was observed between the crisp bread group compared with the two iron-supplemented groups. CONCLUSION: Dietary-based treatment containing heme iron has few side effects and can be used efficiently to improve the iron status of women of reproductive age.

Westernized high-fat diet accelerates weight loss in dextran sulfate sodium-induced colitis in mice, which is further aggravated by supplementation of heme.

The Western diet, rich in fat and red meat, predisposes for inflammatory bowel disease (IBD); however, little is known about mechanisms involved. Red meat contains high levels of heme, a well-known inducer of the cytoprotective enzyme heme oxygenase-1 (HO-1). Pharmacological induction of HO-1 ameliorates experimental colitis. We analyzed the effect of a westernized high-fat (HF) diet supplemented with heme on intestinal HO-1 expression and dextran sulfate sodium (DSS)-induced colitis. Mice were fed chow or HF diets for 2 weeks. In the second week, the HF diet was supplemented with or without 0.5 µmol/g heme. Subsequently, the 3 diet groups were given drinking water with or without 4% DSS to induce colitis. Significant body weight reduction was first observed after 4 days in the chow/DSS mice (-5±3%), whereas this was evident already after 2 days (-6±2%) in HF/DSS mice, showing increased weight loss compared to chow/DSS mice in the following days. Heme supplementation further aggravated DSS-induced weight loss in HF mice (-18±4% vs. -7±5% for HF+heme/DSS vs. HF/DSS, P<.01). Heme increased HO-1 expression in the colon epithelium but decreased villin messenger RNA levels, indicating epithelial damage. In contrast, heme did not affect DSS-induced colon shortening and histological scores of epithelial damage and inflammation. A westernized diet accelerates DSS-induced weight loss in mice, which is further aggravated by heme, despite the induction of HO-1 in the colon epithelium. Our data warrant a detailed analysis of the association of (red) meat-containing diets and the development of IBD.

Non-heme iron as ferrous sulfate does not interact with heme iron absorption in humans.

The absorption of heme iron has been described as distinctly different from that of non-heme iron. Moreover, whether heme and non-heme iron compete for absorption has not been well established. Our objective was to investigate the potential competition between heme and non-heme iron as ferrous sulfate for absorption, when both iron forms are ingested on an empty stomach. Twenty-six healthy nonpregnant women were selected to participate in two iron absorption studies using iron radioactive tracers. We obtained the dose-response curve for absorption of 0.5, 10, 20, and 50 mg heme iron doses, as concentrated red blood cells. Then, we evaluated the absorption of the same doses, but additionally we added non-heme iron, as ferrous sulfate, at constant heme/non-heme iron molar ratio (1:1). Finally, we compare the two curves by a two-way ANOVA. Iron sources were administered on an empty stomach. One factor analysis showed that heme iron absorption was diminished just by increasing total heme iron (P < 0.0001). The addition of non-heme iron as ferrous sulfate did not have any effect on heme iron absorption (P = NS). We reported evidence that heme and non-heme iron as ferrous sulfate does not compete for absorption. The mechanism behind the absorption of these iron sources is not clear.

Heme arginate improves reperfusion patterns after ischemia: a randomized, placebo-controlled trial in healthy male subjects.

BACKGROUND: Heme arginate can induce heme oxygenase-1 to protect tissue against ischemia-reperfusion injury. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging measures changes in tissue oxygenation with a high spatial and temporal resolution. BOLD imaging was applied to test the effect of heme arginate on experimental ischemia reperfusion injury in the calf muscles. METHODS: A two period, controlled, observer blinded, crossover trial was performed in 12 healthy male subjects. Heme arginate (1 mg/kg body weight) or placebo were infused 24 h prior to a 20 min leg ischemia induced by a thigh cuff. 3 Tesla BOLD-imaging of the calf was performed and signal time courses from soleus, gastrocnemius and tibialis anterior muscle were available from 11 participants for technical reasons. RESULTS: Peak reactive hyperemia signal of the musculature was significantly increased and occurred earlier after heme arginate compared to placebo (106.2 ± 0.6% at 175 ± 16s vs. 104.5 ± 0.6% at 221 ± 19s; p = 0.025 for peak reperfusion and p = 0.012 for time to peak). CONCLUSIONS: A single high dose of heme arginate improves reperfusion patterns during ischemia reperfusion injury in humans. BOLD sensitive, functional MRI is applicable for the assessment of experimental ischemia reperfusion injury in skeletal muscle.

A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus.

OBJECTIVE: It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic ß-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM. RESEARCH DESIGN AND METHODS: A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses' Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors. RESULTS: Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87-1.43), 1.31 (1.03-1.68), 1.51 (1.17-1.93), and 1.58 (1.21-2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10-1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk. CONCLUSIONS: These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.

[Pharmacological neuroprotection against brain damage in ischemiai/reperfusion experiment].

Experiment carried out on laboratory animals (rats) were aimed at comparative evaluation of the effect of several neuroprotective drugs under the conditions of model brain ischemia-reperfusion. The experimental methods included staining of brain tissue sections by hematoxiline-eosine, Nissl staining, and expression of NOS1, NOS3, TRAIL by imunnohistological means. The intensity of damage in various parts of brain and the nature of apoptosis without neuroprotection and with popular neuroprotectors (cytoflavin, actovegin, mexidol) and a test drug at the stage ofpreclinical trial (AKF-90-7) were evaluated. Characteristic cytotoxic (coagulative pycnomorphic and colliquative necrosis of neurons) and vascular (hemostasia, erythropedesis) changes were revealed. The neuroprotective effectof drugs decreases in the following order: AKF-90-7 > cytoflavin > actovegin > mexidol.

Bioavailability of a heme-iron concentrate product added to chocolate biscuit filling in adolescent girls living in a rural area of Mexico.

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. The placebo control (PC) group consisted of 35 teenagers with the highest baseline hemoglobin concentrations. The supplemented groups were randomized to receive biscuits fortified with iron sulfate (IS, n = 37) or heme-iron concentrate (HIC, n = 40). Both groups were supplemented with 10.3 mg Fe/d for 7 wk. Blood chemistry and hematology analyses were performed at baseline and at the end of the study. The baseline prevalence of anemia (hemoglobin <12 g/dl) in the entire group was 3.9% and by the end of the study it had fallen to 2.3%. The hemoglobin levels in both supplemented groups increased (P < 0.05) during the study period from 13.6 and 13.5 g/dl for HIC and IS, respectively, at baseline to 14 g/dl at the end of the study. Serum ferritin concentrations decreased by the end of the study in both the PC and IS groups (P < 0.05), but not in the heme group. In conclusion, iron bioavailability from HIC-fortified biscuits was calculated to be 23.7% higher than that observed for IS, as shown by the differences observed in serum ferritin levels during the study. The iron contained in the heme-iron concentrate was well absorbed and tolerated by the adolescents included in the study.

[Neurological complications of acute intermittent porphyria precipitated by porphyrinogenic drugs and efficiency of heme-arginate treatment]. / Complications neurologiques de la porphyrie aiguë intermittente précipitées par les médicaments porphyrinogéniques et efficacité du traitement par l'hème-arginate.

BACKGROUND: Acute intermittent porphyria (AIP) is a rare metabolic disorder of heme biosynthesis characterized by enzymatic defect of porphobiligen desaminase with accumulation and increased excretion of porphyrins and their precursors. Clinical picture is characterized by attacks with a triad of abdominal pain, psychiatric disorder and neurological involvement (central and peripheral). Peripheral nervous system manifestations, often precipitated by porphyrinogenic medications are of poor outcome. AIM: We report a new cases A 13-year-old girl who presented several attacks of AIP and developed acute severe axonal motor neuropathy, three weeks after porphyrinogenic medications (Famotidin, Phenobarbital and Nifedipine). CONCLUSION: We stress on the importance of early diagnosis of AIP to prevent serious neurological complications often precipitated by medications and the efficiency of heme arginate treatment when administrated early during the attacks.