Journal
DRUG METABOLISM AND PHARMACOKINETICS
Volume 24, Issue 5, Pages 438-445Publisher
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.24.438
Keywords
soluble epoxide hydrolase; epoxyeicosatrienoic acid (EET); Cytochrome P450; diabetes; high glucose
Categories
Funding
- Ministry of Education, Science, Culture, Sports and Technology of Japan
Ask authors/readers for more resources
Soluble epoxide hydrolase (sEH) is a xenobiotic-metabolizing enzyme that metabolizes epoxides to produce vicinal diols. Diabetes is a common pathological condition which effects drug metabolism. This study, investigates changes in the levels of sEH in mice with diabetes induced by streptozotocin (STZ). Diabetes reduced the amount of sEH protein in the liver and insulin restored the level of protein. The kidneys are a target of diabetes. Diabetes significantly decreased levels of sEH protein and also mRNA. The distribution of sEH in the kidney was studied with immunostaining. There was distinct staining in the proximal tubules but not in the glomerulus or other regions. Diabetes is characterized by high glucose concentrations that lead to increased production of reactive oxygen species (ROS). High glucose suppressed sEH mRNA and protein expression in Hep3B cells. NADPH oxidase is the main source of ROS generation in high glucose condition. The NADPH oxidase inhibitor, diphenyleneiodonium chloride (DPIC), inhibited decrease in sEH expression at high glucose and hydrogen peroxide suppressed sEH expression. These findings indicate that diabetes reduces sEH expression by inducing ROS and may have important effects on the metabolism of xenobiotics and endogenous substrates of sEH.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available