title: Aspartame Administration and Insulin Treatment Altered Brain Levels of CYP2E1 and CYP3A2 in Streptozotocin-Induced Diabetic Rats.
abstract: This study demonstrates that aspartame consumption and insulin treatment in a juvenile diabetic rat model leads to increase in cytochrome P450 (CYP) 2E1 and CYP3A2 isozymes in brain. Diabetes mellitus was induced in postweaned 21-day-old Wistar male rat by streptozotocin. Animals were randomly assigned to one of the following groups: untreated control, diabetic (D), D-insulin, D-aspartame, or the D-insulin + aspartame-treated group. Brain and liver tissue samples were used to analyze the activity of CYP2E1 and CYP3A2 and protein levels. Our results indicate that combined treatment with insulin and aspartame in juvenile diabetic rats significantly induced CYP2E1 in the cerebrum and cerebellum without modifying it in the liver, while CYP3A2 protein activity increased both in the brain and in the liver. The induction of CYP2E1 in the brain could have important in situ toxicological effects, given that this CYP isoform is capable of bioactivating various toxic substances. Additionally, CYP3A2 induction in the liver and brain could be considered a decisive factor in the variation of drug response and toxicity.
authors.affiliation: Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría (INP), CP 04530, DF, México.
authors.forename: Rosario
authors.initials: R
authors.lastname: Nosti-Palacios
authors.affiliation: Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría (INP), CP 04530, DF, México.
authors.forename: Josefina
authors.initials: J
authors.lastname: Gómez-Garduño
authors.affiliation: Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría (INP), CP 04530, DF, México.
authors.forename: Dora
authors.initials: D
authors.lastname: Molina-Ortiz
authors.affiliation: Servicio de Endocrinología, INP, Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Calzada-León
authors.affiliation: Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría (INP), CP 04530, DF, México.
authors.forename: Víctor Manuel
authors.initials: VM
authors.lastname: Dorado-González
authors.affiliation: Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría (INP), CP 04530, DF, México aritaven@yahoo.com.mx.
authors.forename: Araceli
authors.initials: A
authors.lastname: Vences-Mejía
mesh_terms: D000818:Animals; D001218:Aspartame / Q000009:adverse effects / Q000627:therapeutic use*; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology*; D054022:Cerebrum / Q000187:drug effects / Q000201:enzymology*; D003131:Combined Modality Therapy / Q000009:adverse effects; D019392:Cytochrome P-450 CYP2E1 / Q000737:chemistry / Q000378:metabolism*; D065700:Cytochrome P-450 CYP2E1 Inducers / Q000009:adverse effects / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000378:metabolism*; D065701:Cytochrome P-450 CYP3A Inducers / Q000009:adverse effects / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000178:diet therapy* / Q000188:drug therapy / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D064306:Non-Nutritive Sweeteners / Q000009:adverse effects / Q000627:therapeutic use*; D009928:Organ Specificity; D011897:Random Allocation; D017208:Rats, Wistar
chemical_list: D065700:Cytochrome P-450 CYP2E1 Inducers; D065701:Cytochrome P-450 CYP3A Inducers; D007004:Hypoglycemic Agents; D007328:Insulin; D009419:Nerve Tissue Proteins; D064306:Non-Nutritive Sweeteners; D019392:Cytochrome P-450 CYP2E1; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; D001218:Aspartame
keywords: aspartame; brain; cytochrome P450; diabetes; insulin