Cell-specific activation of aflatoxin B1 correlates with presence of some cytochrome P450 enzymes in olfactory and respiratory tissues in horse

Larsson, Peter; Persson, Eva; Tydén, Eva; Tjälve, Hans

doi:10.1016/s0034-5288(02)00191-1

Cited by 23 publications

(21 citation statements)

References 23 publications

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“…This assumption is supported by results from a study in horses (Larsson et al, 2003). The authors report that the capacity of the lung to activate aflatoxin B 1 (AFB 1 ) by cytochrome P450 enzymes to the reactive intermediate AFB 1 -8,9-epoxide was clearly shown to be lower than those of the liver using microsomal preparations from 5 different horses.…”

Section: Tissue Distribution Of Ketamine and Norketamine Enantiomersmentioning

confidence: 79%

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Knobloch

Portier

Levionnois

et al. 2006

Toxicology and Applied Pharmacology

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Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in subanesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of lowdose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR).A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 μg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies.The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R-and S-ketamine and R-and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R-and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R-and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses).

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Section: Tissue Distribution Of Ketamine and Norketamine Enantiomersmentioning

confidence: 79%

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Knobloch

Portier

Levionnois

et al. 2006

Toxicology and Applied Pharmacology

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“…The target organ in horses, as in all affected animals, is the liver, where the toxin induces centrilobular necrosis (Stoloff and Trucksess, 1979). Horses suffering from aflatoxicosis exhibit non-specific clinical signs, such as inappetence, depression, fever, tremor, ataxia and cough (Larsson et al, 2003). Necropsy findings include yellow-brown liver with centrilobular necrosis, icterus, haemorrhage, tracheal exudates and brown urine (Angsubhakorn et al, 1981;Cysewski et al, 1982;Bortell et al, 1983;Vesonder et al, 1991).…”

Section: Afb1 Toxicity In Equine Speciesmentioning

confidence: 99%

“…Peanut meal and corn were found to be the sources of aflatoxins in Thailand where representative samples of the mixed ration contained approximately 0.2 mg of AFB1 and 0.2 mg of AFB2 per kg (Caloni and Cortinovis, 2011). Larsson et al (2003) suggested a possible link between chronic obstructive pulmonary disease (COPD) and inhaled mycotoxins. A.fumigatus and Mycropolyspora faeni are potential causes of COPD in horses (Halliwell et al, 1993), which is characterised by asthma like symptoms, such as chronic cough, nasal discharge, expiratory dyspnoea and reduced exercise tolerance (Gillespie and Tyler, 1969;Cook, 1976).…”

Section: Aflatoxicosis In Equine Species: Case Reportsmentioning

confidence: 99%

“…The olfactory and respiratory mucosa of horses may be exposed to mycotoxins and other xenobiotics via inhalation of www.intechopen.com contaminated feed-dust particles (Sorensson et al, 1981;Burg and Shotwell, 1984). The inhaled aflatoxins and other xenobiotics may be activated by CYP-enzymes in the epithelial linings of the respiratory tract and contribute to the aetiology of COPD (Larsson et al, 2003;Tydèn et al, 2008).…”

Section: Aflatoxicosis In Equine Species: Case Reportsmentioning

confidence: 99%

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Aflatoxins and Aflatoxicosis in Human and Animals

Dhanasekaran¹,

Shanmugapriya²,

Thajuddin³

et al. 2011

Aflatoxins - Biochemistry and Molecular Biology

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“…The lipophilic nature of AFB 1 facilitates its bioavailability and ease of entry to the bloodstream, organs, and cells. As such, different parts of the human body can be influenced by AFB 1 , including hepatocytes [3], the kidneys [4], respiratory system [5], reproductive system [6], leukocytes [7, 8] and murine neural cells [9]. Limited information is available on the impact of AFB 1 on the human CNS.…”

Section: Introductionmentioning

confidence: 99%

Human Microglial Cells Undergo Proapoptotic Induction and Inflammatory Activation upon in vitro Exposure to a Naturally Occurring Level of Aflatoxin B<sub>1</sub>

Mehrzad

Hosseinkhani

Malvandi

2018

Neuroimmunomodulation

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Objective: Knowledge regarding interactions of AFB₁ with the human nervous system and how a naturally occurring level of AFB₁ could potentially induce neuroimmune dysregulation is very limited. To assess the cellular effects of AFB₁ on the human brain, we used the human microglia cell line CHME5 as a model to pinpoint its potential in vivo translation. Methods: We used the CHME5 cell line culture system, multiplex qPCR, (chemi)bioluminescence, Luminex ELISA, and flow cytometry assays to evaluate the toxic effects of a naturally occurring level of AFB₁ on human microglia. Results: A low concentration of AFB₁ upregulates the mRNA expression of many proinflammatory molecules, such as TLRs, MyD88, NFκB, and CxCr4, induces intracellular ATP depletion, and increases caspase-3/7 activity at different time points following exposure to the toxin. Furthermore, AFB₁-exposed microglia secreted significantly higher levels of IFN-γ and GM-CSF after treatment. We also observed a slight increase in the percentage of apoptotic microglia (annexin V⁺/PI⁻) at 48 h posttreatment. Conclusion: Our work confirmed that the environmentally relevant level of AFB₁ could cause an inflammatory reaction in human microglial cells that is potentially harmful or toxic to the homeostasis of the human central nervous system and might increase susceptibility to neurodegenerative diseases.

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Cell-specific activation of aflatoxin B1 correlates with presence of some cytochrome P450 enzymes in olfactory and respiratory tissues in horse

Cited by 23 publications

References 23 publications

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Aflatoxins and Aflatoxicosis in Human and Animals

Human Microglial Cells Undergo Proapoptotic Induction and Inflammatory Activation upon in vitro Exposure to a Naturally Occurring Level of Aflatoxin B<sub>1</sub>

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