Melatonin modulates drug-induced acute porphyria

Lelli, Sandra M.; Mazzetti, Marta B.; Viale, L

doi:10.1016/j.toxrep.2015.12.010

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…Murine models have suggested a role of melatonin in drug-induced porphyria,26 but it is yet to be investigated in humans. Haemodialysis has also been used with and without human hemin to decrease the levels of PBG and ALA in blood 27 28.…”

Section: Discussionmentioning

confidence: 99%

Paediatric porphyria and human hemin: a treatment challenge in a lower middle income country

et al. 2020

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Here, we report a case of a 15-year-old girl who presented to the emergency department with symptoms of abdominal pain, nausea, vomiting and seizures. She was diagnosed with acute intermittent porphyria. Treatment was started by removing all porphogenic drugs, providing high glucose intake (oral and intravenous), which initially resulted in good clinical outcomes. However, she deteriorated again and also developed neurological manifestation (paraplegia) for which she required mechanical ventilation because of acute respiratory failure. This time she was initiated on human hemin for four consecutive days. After 2 days of therapy, her porphobilinogen levels decreased to 50% of the initial raised value. Increased lactic acid and blood urea nitrogen were the two side effects observed after the treatment, with no apparent signs of acute kidney injury. To the best of our knowledge, in paediatric population, this is the first reported case of treatment of acute intermittent porphyria with human hemin in Pakistan.

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Section: Discussionmentioning

confidence: 99%

Paediatric porphyria and human hemin: a treatment challenge in a lower middle income country

et al. 2020

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“…Previous studies reported that increased concentrations of melatonin act as an antioxidant or antiangiogenic factor in H4IIE and HepG2 hepatoma cells [46–48]. Further, other studies on the therapeutic effect of melatonin on experimental acute porphyria suggested that melatonin enhances PEPCK activity by scavenging reactive oxygen species that peroxidize lipids [49]. Melatonin is absorbed from the intestine and accumulates in the liver via the portal vein.…”

Section: Discussionmentioning

confidence: 99%

Melatonin stimulates transcription of the rat phosphoenolpyruvate carboxykinase gene in hepatic cells

et al. 2020

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“…Interestingly, it has been evidenced that melatonin, a neurohormone with antioxidizing properties and a derivative of serotonin, is able to revert some of the porphyrinogenic toxicity induced by ALA and DDC [ 112 ]. AIP patients are known to have decreased levels of plasma melatonin [ 113 ], a finding which was confirmed in ALA-treated animal models and in pinealocytes cultures [ 85 ].…”

Section: Heme Deficiency-induced Dysfunctionmentioning

confidence: 99%

Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias

et al. 2021

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Porphyrias are a group of congenital and acquired diseases caused by an enzymatic impairment in the biosynthesis of heme. Depending on the specific enzyme involved, different types of porphyrias (i.e., chronic vs. acute, cutaneous vs. neurovisceral, hepatic vs. erythropoietic) are described, with different clinical presentations. Acute hepatic porphyrias (AHPs) are characterized by life-threatening acute neuro-visceral crises (acute porphyric attacks, APAs), featuring a wide range of neuropathic (central, peripheral, autonomic) manifestations. APAs are usually unleashed by external “porphyrinogenic” triggers, which are thought to cause an increased metabolic demand for heme. During APAs, the heme precursors δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) accumulate in the bloodstream and urine. Even though several hypotheses have been developed to explain the protean clinical picture of APAs, the exact mechanism of neuronal damage in AHPs is still a matter of debate. In recent decades, a role has been proposed for oxidative damage caused by ALA, mitochondrial and synaptic ALA toxicity, dysfunction induced by relative heme deficiency on cytochromes and other hemeproteins (i.e., nitric oxide synthases), pyridoxal phosphate functional deficiency, derangements in the metabolic pathways of tryptophan, and other factors. Since the pathway leading to the biosynthesis of heme is inscribed into a complex network of interactions, which also includes some fundamental processes of basal metabolism, a disruption in any of the steps of this pathway is likely to have multiple pathogenic effects. Here, we aim to provide a comprehensive review of the current evidence regarding the mechanisms of neuronal damage in AHPs.

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Melatonin modulates drug-induced acute porphyria

Cited by 5 publications

References 32 publications

Paediatric porphyria and human hemin: a treatment challenge in a lower middle income country

Paediatric porphyria and human hemin: a treatment challenge in a lower middle income country

Melatonin stimulates transcription of the rat phosphoenolpyruvate carboxykinase gene in hepatic cells

Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias

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