Aspartame Administration and Insulin Treatment Altered Brain Levels of CYP2E1 and CYP3A2 in Streptozotocin-Induced Diabetic Rats

Int J Toxicol. 2014 Jul;33(4):325-331. doi: 10.1177/1091581814540480. Epub 2014 Jul 17.

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.

Keywords: aspartame; brain; cytochrome P450; diabetes; insulin.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aspartame / adverse effects
  • Aspartame / therapeutic use*
  • Cerebellum / drug effects
  • Cerebellum / enzymology*
  • Cerebrum / drug effects
  • Cerebrum / enzymology*
  • Combined Modality Therapy / adverse effects
  • Cytochrome P-450 CYP2E1 / chemistry
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Cytochrome P-450 CYP2E1 Inducers / adverse effects
  • Cytochrome P-450 CYP2E1 Inducers / therapeutic use
  • Cytochrome P-450 CYP3A / chemistry
  • Cytochrome P-450 CYP3A / metabolism*
  • Cytochrome P-450 CYP3A Inducers / adverse effects
  • Cytochrome P-450 CYP3A Inducers / therapeutic use
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diet therapy*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism
  • Enzyme Induction / drug effects
  • Hyperglycemia / prevention & control
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Insulin / adverse effects
  • Insulin / therapeutic use
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / enzymology
  • Non-Nutritive Sweeteners / adverse effects
  • Non-Nutritive Sweeteners / therapeutic use*
  • Organ Specificity
  • Random Allocation
  • Rats, Wistar

Substances

  • Cytochrome P-450 CYP2E1 Inducers
  • Cytochrome P-450 CYP3A Inducers
  • Hypoglycemic Agents
  • Insulin
  • Nerve Tissue Proteins
  • Non-Nutritive Sweeteners
  • Cytochrome P-450 CYP2E1
  • Cyp3a2 protein, rat
  • Cytochrome P-450 CYP3A
  • Aspartame