Chloramphenicol Optic Neuropathy

Godel, Victor; Nemet, Pinhas; Lazar, Moshé

doi:10.1001/archopht.1980.01020040269011

Cited by 57 publications

(19 citation statements)

References 11 publications

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“…Transmission electron microscopy of bone marrow cells of patients taking chloramphenicol has shown swollen mitochondria with disrupted cristae and an abnormally high level of intramitochondrial iron deposits, confirming the toxic effect of the drug (69). The clinical findings of chloramphenicol optic neuropathy are characterized by hyperemic optic discs with blurred margins, swelling of the PMB, and central scotomas (70).…”

Section: Chloramphenicolmentioning

confidence: 44%

Drug-Related Mitochondrial Optic Neuropathies

Wang¹,

Sadun²

2013

Journal of Neuro-Ophthalmology

101

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Section: Chloramphenicolmentioning

confidence: 44%

Drug-Related Mitochondrial Optic Neuropathies

Wang¹,

Sadun²

2013

Journal of Neuro-Ophthalmology

101

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“…DDC-treated HEL cells showed very abnormal mitochondria, with condensed distorted cristae or vacuolization very uolization of the cristae and distortion of the inner membrane. In humans, chloramphenicol induces reversible bone marrow toxicity (20) and, rarely, neurotoxicity (peripheral neuropathy [1,18] and optic neuritis [8]). The bone marrow toxicity of chloramphenicol has been associated with mitochondrial ultrastructural abnormalities, producing a condensed configuration of the matrix and cristae (23) or cristae arranged in concentric rings (26).…”

mentioning

confidence: 43%

Ultrastructural changes associated with reduced mitochondrial DNA and impaired mitochondrial function in the presence of 2'3'-dideoxycytidine

Lewis

Hamzeh

Lietman

1992

Antimicrob Agents Chemother

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Incubation of Molt-4 cells in 4 ;LM 2'3'-dideoxycytidine did not produce a significant change in the mitochondrial ultrastructure after 4 days; however, by 12 days, the mitochondrial ultrastructure was distorted, with condensed cristae or vacuolization, or both. Concentration-dependent decreases in both cell growth (mean 50% inhibitory concentration, 4.70 + 0.5 ,uM) and mitochondrial DNA content (mean 50% inhibitory concentration, 0.46 + 0.06 ,uM) occurred after incubation with 2'3'-dideoxycytidine for 4 days.2'3'-Dideoxycytidine (DDC), a deoxynucleoside analog, has activity against human immunodeficiency virus type 1 (HIV-1) in vitro (15) and in vivo (14,25). The selective effect of DDC triphosphate (DDC-TP) on the HIV-1 reverse transcriptase is thought to be due to the lower Ki for the viral reverse transcriptase (Ki = 0.26 ,uM) as opposed to higher Kis for the host nuclear alpha and beta DNA polymerases (Kis = 110 and 2.6 ,uM, respectively) (7, 24). DDC-TP also inhibits the mitochondrial gamma DNA polymerase (Ki = 0.016 ,uM) and does so at concentrations that are comparable to or less than the concentrations necessary to inhibit the viral reverse transcriptase (3, 24). Cells cultured with DDC at concentrations that are comparable to those that can be obtained therapeutically in human plasma (12) produce intracellular concentrations of DDC-TP (4, 24) that are capable of inhibiting the mitochondrial gamma DNA polymerase.The major toxic effect of DDC that limits the dose that can be used is a painful, reversible, primarily sensory peripheral neuropathy, but DDC can also cause granulocytopenia and thrombocytopenia (13). The toxicity of DDC in humans suggests that it must have another site of activity in vivo, apart from inhibiting the HIV-1 reverse transcriptase. Studies of the effect of DDC (and zidovudine [AZT]) on isolated rat liver mitochondria revealed a reduction in the incorporation of radioactive deoxynucleoside triphosphates into mitochondrial DNA (22). DDC-TP caused a reduction of tritiated thymidine uptake by mitochondria isolated from HeLa cells (27). Chen and Cheng (2)

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“…Three young patients suffering from cystic fibrosis of the pancreas and treated with total oral doses of chloramphenicol ranging from 86 to 166 g for a period of three to five months developed optic neuropathy, with blurred vision, loss of visual acuity, visual field defects and colour vision disturbances (Godel et al, 1980). After termination of treatment with the drug, the visual functions partly recovered.…”

Section: Neurotoxicitysupporting

confidence: 40%

Scientific Opinion on Chloramphenicol in food and feed

2014

EFS2

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Chloramphenicol is an antibiotic not authorised for use in food-producing animals in the European Union (EU). However, being produced by soil bacteria, it may occur in plants. The European Commission asked EFSA for a scientific opinion on the risks to human and animal health related to the presence of chloramphenicol in food and feed and whether a reference point for action (RPA) of 0.3 µg/kg is adequate to protect public and animal health. Data on occurrence of chloramphenicol in food extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF) were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which chloramphenicol is present at 0.3 µg/kg in all foods of animal origin, foods containing enzyme preparations and foods which may be contaminated naturally. The mean chronic dietary exposure for this worst-case scenario would range from 11 to 17 and 2.2 to 4.0 ng/kg b.w. per day for toddlers and adults, respectively. The potential dietary exposure of livestock to chloramphenicol was estimated to be below 1 µg/kg b.w. per day. Chloramphenicol is implicated in the generation of aplastic anaemia in humans and causes reproductive/hepatotoxic effects in animals. Margins of exposure for these effects were calculated at 2.4 × 10 5 or greater and the CONTAM Panel concluded that it is unlikely that exposure to food contaminated with chloramphenicol at or below 0.3 µg/kg is a health concern for aplastic anaemia or reproductive/hepatotoxic effects. Chloramphenicol exhibits genotoxicity but, owing to the lack of data, the risk of carcinogenicity cannot be assessed. The SUMMARYChloramphenicol is a broad-spectrum antibiotic effective against Gram-positive and Gram-negative bacteria and, in the past, has been widely used to treat infections in both humans and animals. Chloramphenicol is not authorised for use in food-producing animals in the European Union (EU) but may be used in human medicine and in treatments for non-food-producing animals. Apart from its potential occurrence as a residue in food from illicit treatment of food-producing animals, chloramphenicol has also been used in feed and food enzyme products and may occur naturally in plants from its production by the soil bacterium Streptomyces venezuelae.The EFSA Scientific Opinion entitled "Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin" identified an approach for establishing RPAs for various categories of non-allowed pharmacologically active substances. However, the opinion also identified certain categories of non-allowed pharmacologically active substances that are considered to be outside the scope of the procedure, including substances causing blood dyscrasias (aplastic anaemia) such as chloramphenicol. As chloramphenicol is excluded fro...

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Chloramphenicol Optic Neuropathy

Cited by 57 publications

References 11 publications

Drug-Related Mitochondrial Optic Neuropathies

Drug-Related Mitochondrial Optic Neuropathies

Ultrastructural changes associated with reduced mitochondrial DNA and impaired mitochondrial function in the presence of 2'3'-dideoxycytidine

Scientific Opinion on Chloramphenicol in food and feed

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