Genotoxicity and pharmacokinetic characterization of Cereus jamacaru ethanolic extract in rats

Author:

de Medeiros Iris Ucella1,de Medeiros Rhoza Araújo1,Bortolin Raul Henandes1,de Queiroz Fernando Márlisson2,Silbiger Vivian Nogueira13,Pflugmacher Stephan4,Schwarz Aline13

Affiliation:

1. Post Graduation Program in Pharmaceutical Science, Federal University of Rio Grande do Norte, Natal, Brazil

2. Pharmacy student, Federal University of Rio Grande do Norte, Natal, Brazil

3. Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Brazil

4. Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany

Abstract

Abstract The effect of Cereus jamacaru ethanolic extract in rats was analyzed using genotoxicity assays and liver ABCB1 and CYP2D4 gene expression. The lyophilized extract of C. jamacaru cladodes was analyzed with LC–MS/MS. Male Wistar rats (n=36) were equally distributed into six groups that did (+) or did not (−) receive cyclophosphamide treatments: Control (−); Control (+); EXP 1 (−), and EXP 1 (+), both treated with 210 mg/kg of ethanolic extract; and EXP 2 (−) and EXP 2 (+), both treated with 420 mg/kg of ethanolic extract. After 30 d of treatment, body weight and food and water intake were monitored. Right femur of the rats and spinal canal fluid were harvested and used for genotoxicity assays, and the liver samples were used for gene expression studies. The phytochemical analysis identified novel compounds. Animals treated with C. jamacaru showed lower body weight and food ingestion compared to controls (P<0.05). The genotoxicity assay showed an absence of ethanolic extract cytotoxicity. CYP2D4 expression was higher in EXP 2 groups compared with EXP 1 (−) group (P<0.05). ABCB1A expression was higher in negative groups compared with the positive groups. These results indicated a new phytochemical characterization of C. jamacaru and its effect on food ingestion and body weight gain. Moreover, the genotoxicity assay suggested that C. jamacaru ethanolic extract treatment presents significant intrinsic genotoxic potential and the enhanced expression of ABCB1 and CYP2D4 on C. jamacaru extract treatment suggests a role of the efflux transporter and microsomal enzyme, respectively, in C. jamacaru pharmacokinetics.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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