Influence of Chloramphenicol on Rat Hepatic Microsomal Components and Biomarkers of Oxidative Stress: Protective Role of Antioxidants

Farombi, E. Olatunde; Adaramoye, Oluwatosin A.; Emerole, Godwin O.

doi:10.1034/j.1600-0773.2002.910307.x

Cited by 17 publications

(14 citation statements)

References 36 publications

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“…The objective of the present investigation was established taking into consideration work done on the haematotoxic effects of chloramphenicol and its ability to induce oxidative alterations in hepatic cells [20]. On the basis of these previous studies, the present work was carried out with the purpose of evaluating both the capacity of chloramphenicol to generate reactive species in human neutrophils, and also the antioxidant response by superoxide dismutase (SOD), diaphorase, catalase (CAT) and reduced glutathione (GSH).…”

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confidence: 99%

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Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Páez

Becerra

Albesa

2008

Basic Clin Pharma Tox

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The aim of this study was to evaluate the in vitro effect of chloramphenicol in order to determine its potential toxic effects on human neutrophils, by using assays of reactive oxygen species (ROS) determination, nitrite measurement and antioxidant systems. Chloramphenicol enabled the oxidative stress response of neutrophils and increased the ROS production at 2, 4, 8 and 16 μ g/ml, while ROS generation decreased at high concentrations (32 μ g/ml). The nitroblue tetrazolium assay shows that neutrophils incubated with chloramphenicol increased the intracellular ROS, with the extracellular production rising with a corresponding increase in antibiotic concentration. Enzymatic activities -superoxide dismutase, catalase and diaphorase enzymes -increased after chloramphenicol treatment, while the glutathione level decreased in neutrophils incubated with antibiotic. The results obtained in the present work suggest that the study of susceptibility to oxidative stress in neutrophils before chloramphenicol treatment could be adequate for in vitro toxicity screening.Oxidative stress has been associated with hepatic and renal toxicity [1], but leucocytes can also be affected in the reactive oxygen species (ROS) production by toxic substances [2]. The regulation of ROS production is particularly important in neutrophils, because these cells perform an important function in host defence against bacterial infections by producing ROS and nitrogen species, hydrolytic and proteolytic enzymes, and antimicrobial polypeptides. Although neutrophils also produce nitric oxide, the levels are low and likely to result from the activity of a constitutive nitric oxide synthase [3]. Deregulation of nitric oxide and increased oxidative and nitrosative stress are implicated in tissue damage [4].Several chemical agents can alter the cellular functions associated with the oxidative metabolism, thereby stimulating ROS production in neutrophils [5]. Antibiotics have various side effects, and some of them may influence the functions of neutrophils [6]. Free radical reactions have been suggested to be involved in the toxic effects of several antibiotics [7][8][9][10][11]. Idiosyncratic aplastic anaemia can occur in predisposed patients after chloramphenicol, irrespective of the dosage. This is thought to be due to the production by the gut flora of a nitro-reduction derivative of chloramphenicol. This derivative can induce DNA damage in replicating haematopoietic stem cells, resulting in marrow hypocellularity and progressive pancytopaenia [12]. The most common presentation, however, is a reversible, dose-dependent bone marrow suppression, which usually occurs when serum chloramphenicol levels exceed 25 mg/l for prolonged periods of time. This condition is associated with the inhibition of mitochondrial protein synthesis, and is characterized by mild marrow hypocellularity, anaemia, neutropaenia and thrombocytopaenia [13]. As non-idiosyncratic aplastic anaemia and 'grey baby' syndrome are dose-dependent complications of chloramphenicol us...

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“…Similarly, some antibiotics seem to affect the oxidative state of cellular components; for example, the action of chloramphenicol on cytochrome P450. This is related to enzymatic oxidation, via an increase in ROS, while the coadministration of antioxidant vitamins may attenuate its toxic action [20].…”

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Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Páez

Becerra

Albesa

2008

Basic Clin Pharma Tox

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“…Chloramphenicol has been demonstrated to affect the oxidative state of cellular components by increasing the intracellular ROS, while the glutathione level decreased in neutrophils [94] [109].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Some Antibiotics in Curing Resistant <i>Escherichia coli</i> Infection

El-Banna¹,

El-Aziz²,

El-Mahdy³

et al. 2015

JBM

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There is growing interest in re-evaluation of older antibiotics with the wide spread of pathogen resistance, especially gram negative bacteria, which impair treatment of some infections. In contrast various studies have reported that some antibiotics have efficacy in clearing resistant bacterial infections. On account of that it was interesting to evaluate the efficacy of erythromycin, chloramphenicol and/or tenoxicam in curing and/or relieving wound infection of highly resistant Escherichia coli and investigate the possible mechanisms beyond their antibacterial activity. This was achieved through evaluating highly resistant E. coli strains in vitro using agar dilution and in vivo rat models of E. coli infected wound and acute inflammation by carrageenin, where possible mechanisms were evaluated through measuring immunological mediators and histopathological examination. This study revealed that in vivo, erythromycin alone or in combination with tenoxicam significantly improved the healing of infected skin wounds with E. coli irresspective of resistancy in vitro. In addition to the improvement of immunological mediators involved in inflammatory reaction, oxidative stress and in cytokines expression as response to the bacterial infection in vivo. On the other hand chloramphenicol neither alone nor in combination with tenoxicam, achieved any significant effect. Tenoxicam didn't show antimicrobial activity alone nor in combination with tested antibiotics in vitro, but it has shown synergestic activity in combination with tested antibiotics in vivo. Thus we concluded that immunomodulatory activity of erythromycin through anti-inflammatory and antioxidant effects was the possible mechanisms by which this antibiotic had healed infection with resistant E. coli in vivo, despite its resistancy to this antibiotic in vitro.

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“…In an in vitro study, reported in the same paper, chloramphenicol at concentrations between 0.001 and 0.1 mM inhibited the activity of the same enzymes, with the exception of ethoxyresorufin O-deethylase. In an additional study, in which rats (n = 5) were treated orally with 28 mg/kg chloramphenicol succinate for 10 consecutive days, an increase in liver microsomal malondialdehyde and lipid hydroperoxide was observed, indicating induction of lipid peroxidation by chloramphenicol (Farombi et al, 2002). Ebaid et al (2011) treated rats orally with either saline (control), chloramphenicol sodium succinate (86 mg/kg) for 21 days, chloramphenicol sodium succinate (86 mg/kg) for 21 days followed by Nigella sativa oil for 30 days or combined exposure of chloramphenicol sodium succinate (86 mg/kg) and N. sativa for 21 days.…”

Section: Repeated Dose Toxicitymentioning

confidence: 99%

“…Furthermore, chloramphenicol treatment caused damage in enterocytes. Farombi et al (2002) investigated the effect of chloramphenicol succinate on the microsomal drug oxidising system in vivo and in vitro. Male Wistar albino rats (n = 5) were treated orally with chloramphenicol succinate at doses of 28, 57 or 86 mg/kg b.w.…”

Section: Repeated Dose Toxicitymentioning

confidence: 99%

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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Influence of Chloramphenicol on Rat Hepatic Microsomal Components and Biomarkers of Oxidative Stress: Protective Role of Antioxidants

Cited by 17 publications

References 36 publications

Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Efficacy of Some Antibiotics in Curing Resistant <i>Escherichia coli</i> Infection

Scientific Opinion on Chloramphenicol in food and feed

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Influence of Chloramphenicol on Rat Hepatic Microsomal Components and Biomarkers of Oxidative Stress: Protective Role of Antioxidants

Cited by 17 publications

References 36 publications

Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Chloramphenicol‐Induced Oxidative Stress in Human Neutrophils

Efficacy of Some Antibiotics in Curing Resistant &lt;i&gt;Escherichia coli&lt;/i&gt; Infection

Scientific Opinion on Chloramphenicol in food and feed

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Efficacy of Some Antibiotics in Curing Resistant <i>Escherichia coli</i> Infection