The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria

Tishler, Peter V.

doi:10.1016/s0024-3205(99)00237-4

Cited by 8 publications

(4 citation statements)

References 16 publications

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“…PPIX is often used in PDT because it is not only effective, but it also selectively accumulates in certain tumor cells, one probable reason being that another enzyme involved in the biosynthesis of heme (5), porphobilinogen deaminase (PBGD), has a higher activity in certain tumor cells than in healthy cells (6). Other enzymes, such as AS and ferrochelatase (7,8), also seem to have differential activity in healthy and tumor cells, and may also contribute to the increased concentration of PPIX in tumor cells compared with neighboring healthy tissue (9).…”

Section: Introductionmentioning

confidence: 99%

On the Role of Iron and one of its Chelating Agents in the Production of Protoporphyrin IX Generated by 5‐Aminolevulinic Acid and its Hexyl Ester Derivative Tested on an Epidermal Equivalent of Human Skin

Uehlinger

Ballini

Bergh

et al. 2006

Photochem & Photobiology

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Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) or its derivatives as precursors of protoporphyrin IX (PPIX) is routinely used in dermatology for the treatment of various pathologies. However, this methodology suffers to some extent from a limited efficacy. Therefore, the main goal of this study was to investigate the modulation and pharmacokinetics of PPIX buildup after a 5 h incubation with ALA (1.5 mM) and one of its derivatives, the hexyl ester of ALA (h-ALA) (1.5 mM), on the human epidermal equivalent Epidex. PPIX production was modulated with (L+) ascorbic acid iron (II) salt (LAI) or the iron (II)-specific chelating agent deferoxamine (DFO). PPIX fluorescence from the Epidex layers was measured up to 150 h after the precursor administration using a microspectrofluorometer (lambda(ex): 400 +/- 20 nm; lambda(det): 635 nm). The maximum PPIX fluorescence intensity induced by h-ALA was about 1.7 x larger than that induced by ALA. The addition of DFO resulted in a more than 50% increase in PPIX fluorescence for both precursors. The decay half life measured for PPIX fluorescence is 30 and 42.5 h, respectively, for ALA and h-ALA. These half lives are doubled when the samples contain DFO. In the samples with the highest fluorescence intensity, a modified fluorescence spectrum was observed after 10 h, with the emergence of a peak at 590 nm, which is attributed to zinc protoporphyrin IX (Zn PPIX).

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Section: Introductionmentioning

confidence: 99%

On the Role of Iron and one of its Chelating Agents in the Production of Protoporphyrin IX Generated by 5‐Aminolevulinic Acid and its Hexyl Ester Derivative Tested on an Epidermal Equivalent of Human Skin

Uehlinger

Ballini

Bergh

et al. 2006

Photochem & Photobiology

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“…[53][54][55] Sulfonamide-containing antibiotics, such as sulfamethoxazole and sulfisoxazole, have been considered to be risky for use in patients with AHP according to the American Porphyria Foundation Drug Database [https://porph yriaf ounda tion.org/drugd ataba se/]; however, in our LMH cell system, neither of these drugs led to excess PP accumulation, even in the presence of DFO (Figure 2). Indeed, our recent [November 3, 2021] PubMed searches on "sulfisoxazole AND acute porphyria" yielded only one citation, 56 which concluded that sulfisoxazole did not affect the activity of hydroxymethylbilane synthase in human erythrocytes or rat livers. A search on" sulfamethoxazole AND acute porphyria" did not yield any citations.…”

Section: Discussionmentioning

confidence: 99%

Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence‐based screening assay

Christopher

Horn

Wan

et al. 2022

Pharmacology Res & Perspec

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Compounds that induce 5‐aminolevulinic acid [ALA] synthase‐1 and/or cytochromes P‐450 may induce acute porphyric attacks in patients with the acute hepatic porphyrias [AHPs]. Currently, there is no simple, robust model used to assess and predict the porphyrogenicity of drugs and chemicals. Our aim was to develop a fluorescence‐based in vitro assay for this purpose. We studied four different hepatic cell culture models: HepG2 cells, LMH cells, 3D HepG2 organoids, and 3D organoids of primary liver cells from people without known disease [normal human controls]. We took advantage of the fluorescent properties of protoporphyrin IX [PP], the last intermediate of the heme biosynthesis pathway, performing fluorescence spectrometry to measure the intensity of fluorescence emitted by these cells treated with selected compounds of importance to patients with AHPs. Among the four cell culture models, the LMH cells produced the highest fluorescence readings, suggesting that these cells retain more robust heme biosynthesis enzymes or that the other cell models may have lost their inducibility of ALA synthase‐1 [ALAS‐1]. Allyl isopropyl acetamide [AIA], a known potent porphyrogen and inducer of ALAS‐1, was used as a positive control to help predict porphyrogenicity for tested compounds. Among the tested compounds (acetaminophen, acetylsalicylic acid, β‐estradiol, hydroxychloroquine sulfate, alpha‐methyldopa, D (‐) norgestrel, phenobarbital, phenytoin, sulfamethoxazole, sulfisoxazole, sodium valproate, and valsartan), concentrations greater than 0.314 mM for norgestrel, phenobarbital, phenytoin, and sodium valproate produced fluorescence readings higher than the reading produced by the positive AIA control. Porphyrin accumulation was also measured by HPLC to confirm the validity of the assay. We conclude that LMH cell cultures in multi‐well plates are an inexpensive, robust, and simple system to predict the porphyrogenicity of existing or novel compounds that may exacerbate the AHPs.

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“…Taşikardisi ve hipertansiyonu propranolol ve enapril tedavisi ile kontrol altına alındı. Bu hastalarda atak esnasında görülen afebril nöbetlere müdahale etmek için kullanılan antikonvülzanlar hayati tehlike yaratabilir (5). Zaten respiratuar kas güçsüzlüğü olan porfiria olgularının antikonvülzan ile solunumu deprese olup, gelişen solunum yetmezliği ölüm nedeni olabilir.…”

Section: Discussionunclassified

A Rare Cause of Convulsions in Children Acute Intermittent Porphyria: A Case Report

Yıldırım

Polat

Yazici

et al. 2022

Hitit Medical Journal

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Porfiriler hem biyosentezinde görevli enzimlerin doğuştan yada kazanılmış bozukluğu, yada eksikliği sonucu oluşan, periferik ve santral sinir sistemini etkileyebilen, farklı alt tipleri olan, nadir görülen metabolik hastalıklardır. Akut intermittan porfiri, porfirilerin en yaygın görülen tipidir ve nöropsikyatrik belirtilerle birlikte açıklanamayan karın ağrısı olan hastalarda ayırıcı tanıda düşünülmelidir. Posterior reversible ensefalopati sendromu (PRES) ise baş ağrısı, mental durum değişiklikleri, görme bozuklukları, mide bulantısı, parezi ve yaygın nöbetler gibi semptomlara hipertansiyonun eşlik ettiği klinik ve radyolojik bir durumdur. Bu yazıda karın ağrısı ve konvulsiyon nedeni ile acil servise başvuran, sonrasında akut intermittan porfiri ve akut intermittan porfiri ile ilişkili PRES tanısı alan hasta, nadir görülmesi nedeni ile sunulmuştur.

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The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria

Cited by 8 publications

References 16 publications

On the Role of Iron and one of its Chelating Agents in the Production of Protoporphyrin IX Generated by 5‐Aminolevulinic Acid and its Hexyl Ester Derivative Tested on an Epidermal Equivalent of Human Skin

On the Role of Iron and one of its Chelating Agents in the Production of Protoporphyrin IX Generated by 5‐Aminolevulinic Acid and its Hexyl Ester Derivative Tested on an Epidermal Equivalent of Human Skin

Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence‐based screening assay

A Rare Cause of Convulsions in Children Acute Intermittent Porphyria: A Case Report

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