Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo

•Piperine was negative in an in vivo MNT in bone marrow cells up to the MTD.•Piperine is not genotoxic in CHO cells.•The hypothermic and hematotoxic effects of piperine did not results in increased micronuclei frequencies in the in vivo MNT. Piperine is responsible for the hot taste of black pepper....

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Veröffentlicht in:Food and chemical toxicology 2014-04, Vol.66, p.350-357
Hauptverfasser: Thiel, Anette, Buskens, Carin, Woehrle, Tina, Etheve, Stéphane, Schoenmakers, Ankie, Fehr, Markus, Beilstein, Paul
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container_title Food and chemical toxicology
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creator Thiel, Anette
Buskens, Carin
Woehrle, Tina
Etheve, Stéphane
Schoenmakers, Ankie
Fehr, Markus
Beilstein, Paul
description •Piperine was negative in an in vivo MNT in bone marrow cells up to the MTD.•Piperine is not genotoxic in CHO cells.•The hypothermic and hematotoxic effects of piperine did not results in increased micronuclei frequencies in the in vivo MNT. Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published. To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed. Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic.
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Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published. To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed. Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. 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Additionally an in vitro MNT in Chinese hamster ovary cells was performed. Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. 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subjects Alkaloids - toxicity
Animals
Benzodioxoles - toxicity
Biological and medical sciences
Black pepper
CHO Cells
Cricetinae
Cricetulus
Female
Food toxicology
Genotoxicity
In Vitro Techniques
Male
Medical sciences
Mice
Micronucleus
Mutagenicity Tests
Piper nigrum
Piper nigrum - chemistry
Piperidines - toxicity
Piperine
Polyunsaturated Alkamides - toxicity
Toxicology
title Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo
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