Erythromycin as a potential precipitating agent in the onset of Leber's hereditary optic neuropathy

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Abstract

A 23-years-old male entered a safety clinical trial for cetirizine (a selective histamine H1-receptor antagonist) in combination with the antibiotic erythromycin. Within a few weeks of finishing the trial, the patient reported bilateral vision loss with optic nerve atrophy. Genetic studies showed that he had a mitochondrial DNA (mtDNA) mutation at position 11778 (within the gene for subunit 4 of NADH-coenzyme Q oxidoreductase), commonly associated with Leber's hereditary optic neuropathy. To test if erythromycin could worsen the mitochondrial respiratory chain defect associated with the 11778 mtDNA mutation, we transferred the patient's mtDNA to cultured mtDNA-less osteosarcoma cells. Erythromycin inhibited proliferation of the patient's transmitochondrial cybrids in conditions that required mitochondrial respiration for growth. We confirmed that erythromycin is a potent inhibitor of mitochondrial translation in these cells. Taken together, these results suggest that erythromycin may have hastened a bioenergetics crisis in the optic nerve of this patient. This association underscores the importance of being cautious with the use of drugs that interfere with cellular respiration in individuals with an underlying mitochondrial dysfunction.

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalMitochondrion
Volume4
Issue number1
DOIs
StatePublished - Jun 1 2004

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Leber's Hereditary Optic Atrophy
Erythromycin
Mitochondrial DNA
Optic Nerve
Cetirizine
Histamine H1 Antagonists
Cell Respiration
Optic Atrophy
Mutation
Ubiquinone
Osteosarcoma
Electron Transport
NAD
Energy Metabolism
Oxidoreductases
Respiration
Clinical Trials
Anti-Bacterial Agents
Safety
Growth

Keywords

  • Erythromycin
  • Leber's hereditary optic neuropathy
  • Transmitochondrial cybrids

ASJC Scopus subject areas

  • Biophysics

Cite this

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abstract = "A 23-years-old male entered a safety clinical trial for cetirizine (a selective histamine H1-receptor antagonist) in combination with the antibiotic erythromycin. Within a few weeks of finishing the trial, the patient reported bilateral vision loss with optic nerve atrophy. Genetic studies showed that he had a mitochondrial DNA (mtDNA) mutation at position 11778 (within the gene for subunit 4 of NADH-coenzyme Q oxidoreductase), commonly associated with Leber's hereditary optic neuropathy. To test if erythromycin could worsen the mitochondrial respiratory chain defect associated with the 11778 mtDNA mutation, we transferred the patient's mtDNA to cultured mtDNA-less osteosarcoma cells. Erythromycin inhibited proliferation of the patient's transmitochondrial cybrids in conditions that required mitochondrial respiration for growth. We confirmed that erythromycin is a potent inhibitor of mitochondrial translation in these cells. Taken together, these results suggest that erythromycin may have hastened a bioenergetics crisis in the optic nerve of this patient. This association underscores the importance of being cautious with the use of drugs that interfere with cellular respiration in individuals with an underlying mitochondrial dysfunction.",
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AU - Moraes, Carlos T

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N2 - A 23-years-old male entered a safety clinical trial for cetirizine (a selective histamine H1-receptor antagonist) in combination with the antibiotic erythromycin. Within a few weeks of finishing the trial, the patient reported bilateral vision loss with optic nerve atrophy. Genetic studies showed that he had a mitochondrial DNA (mtDNA) mutation at position 11778 (within the gene for subunit 4 of NADH-coenzyme Q oxidoreductase), commonly associated with Leber's hereditary optic neuropathy. To test if erythromycin could worsen the mitochondrial respiratory chain defect associated with the 11778 mtDNA mutation, we transferred the patient's mtDNA to cultured mtDNA-less osteosarcoma cells. Erythromycin inhibited proliferation of the patient's transmitochondrial cybrids in conditions that required mitochondrial respiration for growth. We confirmed that erythromycin is a potent inhibitor of mitochondrial translation in these cells. Taken together, these results suggest that erythromycin may have hastened a bioenergetics crisis in the optic nerve of this patient. This association underscores the importance of being cautious with the use of drugs that interfere with cellular respiration in individuals with an underlying mitochondrial dysfunction.

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