Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes
Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intest...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00018/full |
| _version_ | 1818942892907954176 |
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| author | Barbara Pavan Alessandro Dalpiaz Luca Marani Sarah Beggiato Luca Ferraro Donatella Canistro Moreno Paolini Fabio Vivarelli Maria C. Valerii Antonietta Comparone Luigia De Fazio Enzo Spisni |
| author_facet | Barbara Pavan Alessandro Dalpiaz Luca Marani Sarah Beggiato Luca Ferraro Donatella Canistro Moreno Paolini Fabio Vivarelli Maria C. Valerii Antonietta Comparone Luigia De Fazio Enzo Spisni |
| author_sort | Barbara Pavan |
| collection | DOAJ |
| description | Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T07:18:39Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c9273bbdbec84f72a2e3052e40504ee82022-12-21T19:48:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-01-01910.3389/fphar.2018.00018332229Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing EnzymesBarbara Pavan0Alessandro Dalpiaz1Luca Marani2Sarah Beggiato3Luca Ferraro4Donatella Canistro5Moreno Paolini6Fabio Vivarelli7Maria C. Valerii8Antonietta Comparone9Luigia De Fazio10Enzo Spisni11Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, Alma Mater Studiorum, University of Bologna, Bologna, ItalyGeraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.http://journal.frontiersin.org/article/10.3389/fphar.2018.00018/fullgeraniolgutbioavailabilitypharmacokineticsxenobiotic-metabolizing enzymes |
| spellingShingle | Barbara Pavan Alessandro Dalpiaz Luca Marani Sarah Beggiato Luca Ferraro Donatella Canistro Moreno Paolini Fabio Vivarelli Maria C. Valerii Antonietta Comparone Luigia De Fazio Enzo Spisni Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes Frontiers in Pharmacology geraniol gut bioavailability pharmacokinetics xenobiotic-metabolizing enzymes |
| title | Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes |
| title_full | Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes |
| title_fullStr | Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes |
| title_full_unstemmed | Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes |
| title_short | Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes |
| title_sort | geraniol pharmacokinetics bioavailability and its multiple effects on the liver antioxidant and xenobiotic metabolizing enzymes |
| topic | geraniol gut bioavailability pharmacokinetics xenobiotic-metabolizing enzymes |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2018.00018/full |
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