Journal of Clinical Toxicology
Open Access
ISSN: 2161-0495
ISSN: 2161-0495
Heike Wulff
Tanzania
Research Article
Inhibition of Soluble Epoxide Hydrolase as a Novel Approach to High Dose
Diazepam Induced Hypotension
Author(s): Arzu Ulu, Bora Inceoglu, Jun Yang, Vikrant Singh, Stephen Vito, Heike Wulff and Bruce D HammockArzu Ulu, Bora Inceoglu, Jun Yang, Vikrant Singh, Stephen Vito, Heike Wulff and Bruce D Hammock
Context: Hypotension is one of the dose limiting side effects of benzodiazepines (BZDs), in particular of diazepam (DZP) which is still widely used in the clinic. Currently, only one FDA approved antidote exists for BZD overdose and novel approaches are needed to improve management of DZP overdose, dependency and withdrawal. Objective: Here, we hypothesized that increasing bioactive lipid mediators termed epoxy fatty acids (EpFAs) will prevent hypotension, as was shown previously in a murine model of LPS-induced hypotension. Therefore, we first characterized the time and dose dependent profile of DZP induced hypotension in mice, and then investigated the reversal of the hypotensive effect by inhibiting the soluble epoxide hydrolase (sEH), an enzyme that regulates the levels of EpFAs. Materials and Methods: Following baseline systolic BP recording using tail cuffs, mice were administer.. View More»
DOI:
10.4172/2161-0495.1000300