Genotoxic effect of alkaloids

Henriques, João Antônio Pêgas; Moreno, Paulo Roberto Hrihorowitsch; Poser, Gilsane Lino von; Querol, C. C.; Henriques, A. T.

doi:10.1590/s0074-02761991000600018

Cited by 11 publications

(5 citation statements)

References 5 publications

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“…It has been suggested that alkaloids are potentially mutagenic, because their therapeutic actions involve interactions with DNA [4,[40][41][42]. This possibility was corroborated in the present study only when mice were submitted to the highest dose of isatin (150 mg/kg b.w.)…”

Section: Discussionsupporting

confidence: 83%

Mutagenicity and genotoxicity of isatin in mammalian cells in vivo

Cândido-Bacani

Reis

Serpeloni

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Isatin (1H-indole-2,3-dione) is a synthetically versatile substrate used for the synthesis of heterocyclic compounds and as a raw material for drug synthesis. Isatin and its derivatives demonstrate anticonvulsant, antibacterial, antifungal, antiviral, and anticancer properties. We evaluated the genotoxic and mutagenic effects of acute (24h) and repeated (14d) exposure to isatin in vivo, using the comet assay and the micronucleus test. Three doses (50, 100, and 150mg/kgb.w.) were administered to mice via gavage. Doses were selected according to the LD(50) of isatin, estimated in a preliminary test to be 1g/kgb.w. To evaluate the results, parametric (ANOVA/Tukey) and non-parametric (Kruskal-Wallis/Dunn's post hoc test) tests were used, according to the nature of the data distribution. At all doses (50, 100 and 150mg/kgb.w.), after acute treatment with isatin, alterations in DNA migration (comet assay) were not observed and mutagenic effects were not seen (micronucleus test on peripheral blood cells). After repeated doses, only the highest dose of isatin (150mg/kgb.w.) induced alterations in the DNA that gave rise to micronuclei in the bone marrow and peripheral blood cells of the mice. Our results show that the mutagenic and genotoxic effects of isatin depend on dose and on period of exposure.

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Section: Discussionsupporting

confidence: 83%

Mutagenicity and genotoxicity of isatin in mammalian cells in vivo

Cândido-Bacani

Reis

Serpeloni

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…The mechanisms of its action included the suppression of TNF -α and IL -6 gene transcription, the inhibition of the production of NO, prostaglandin E2, and superoxide anions, as well as elastase-release [ 1 , 10 , 11 ]. Furthermore, skimmianine also exhibited cytotoxicity against a variety of cancer cell lines [ 12 , 13 , 14 , 15 ] and genotoxicity [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

Zhan

Chen

et al. 2017

Molecules

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Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite profiling of skimmianine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilotTM software. These predicted metabolites were further analyzed by MS2 spectra, and compared with the detailed fragmentation pathway of the skimmianine standard and literature data. A total of 16 metabolites were identified for the first time in rat plasma, urine, and feces samples after oral administration of skimmianine. Skimmianine underwent extensive Phase I and Phase II metabolism in rats. The Phase I biotransformations of skimmianine consist of epoxidation of olefin on its furan ring (M1) followed by the hydrolysis of the epoxide ring (M4), hydroxylation (M2, M3), O-demethylation (M5-M7), didemethylation (M14–M16). The Phase II biotransformations include glucuronide conjugation (M8–M10) and sulfate conjugation (M11–M13). The epoxidation of 2,3-olefinic bond followed by the hydrolysis of the epoxide ring and O-demethylation were the major metabolic pathways of skimmianine. The results provide key information for understanding the biotransformation processes of skimmianine and the related furoquinoline alkaloids.

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“…Chelerythrine-induced disintegration of the mitochondrial genome in S. cerevisiae, demonstrated for the first time in this paper, can be explained by the intercalative binding of the alkaloid to mitochondrial DNA [9]. This mutagenic effect of chelerythrine in yeast is in contrast to a recent study failing to demonstrate its genotoxic and mutagenic activity in Escherichia coli [13] and should be taken into consideration for the longterm medical use of this phytotherapeutic.…”

Section: Omentioning

confidence: 88%

Induction of respiration-deficient mutants inSaccharomyces cerevisiaeby chelerythrine

Krivjanský

Obernauerová

Ulrichová

et al. 1994

FEMS Microbiology Letters

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Chelerythrine and sanguinarine, two structurally related benzo/c/phenanthridine alkaloids, prevented growth of yeast cells in medium containing either glucose or non-fermentable carbon sources. At concentrations permitting growth of the yeast Saccharomyces cerevisiae, chelerythrine, but not sanquinarine, induced cytoplasmic respiration-deficient mutants. The petite clones that were analysed exhibited suppressiveness and contained different fragments of the wild-type mitochondrial genome.

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Genotoxic effect of alkaloids

Cited by 11 publications

References 5 publications

Mutagenicity and genotoxicity of isatin in mammalian cells in vivo

Mutagenicity and genotoxicity of isatin in mammalian cells in vivo

Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

Induction of respiration-deficient mutants inSaccharomyces cerevisiaeby chelerythrine

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