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Effect of status epilepticus on expression of brain UDP‐glucuronosyltransferase 1a in rats
Author(s) -
Asai Yuki,
Tanaka Hatsuna,
Nadai Masayuki,
Katoh Miki
Publication year - 2018
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2114
Subject(s) - status epilepticus , kainic acid , oxidative stress , glucuronidation , hippocampus , heme oxygenase , medicine , cortex (anatomy) , endocrinology , glucuronosyltransferase , cerebral cortex , epilepsy , diazepam , pharmacology , chemistry , heme , biology , biochemistry , receptor , neuroscience , microsome , enzyme , glutamate receptor
Status epilepticus (SE) involves severe epileptic seizures that cause oxidative stress in the brain. Oxidative stress is known to influence uridine 5'‐diposphate‐glucuronosyltransferase (UGT) 1A expression. The present study aimed at elucidating the effect of SE on Ugt1a1, Ugt1a6 and Ugt1a7 expression in the rat brain. Kainic acid was used to create an animal model of SE. Sprague‐Dawley rats were treated intraperitoneally with 10 mg/kg kainic acid. Ugt1a1 and Ugt1a7 mRNA levels were increased by SE in the cortex and hippocampus (Ugt1a1: 4.0‐ and 5.3‐fold, respectively; Ugt1a7: 2.8‐ and 2.5‐fold, respectively). Moreover, the induction degree of heme oxygenase‐1 mRNA, an oxidative stress marker, was high in these regions, suggesting that oxidative stress could be involved in Ugt1a1 and Ugt1a7 induction. Ugt1a6 was elevated by 1.8‐fold in the cortex in both SE and non‐response (non‐epileptic seizure response) rats, implying that Ugt1a6 induction may be independent from SE. An intraperitoneal single administration of 25 mg/kg diazepam (DZP) for the treatment of SE could attenuate heme oxygenase‐1 induction in the cortex, whereas Ugt1a1 was decreased in the hippocampus, but not in the cortex, suggesting that there likely exists an alternative mechanism for Ugt1a1 reduction by DZP treatment. Continuous 14‐day administration of DZP inhibited Ugt1a1 induction in the cortex, but did not have an effect on Ugt1a7 induction. This study indicated that SE altered the expression of brain Ugt1a1 and Ugt1a7, which could alter glucuronidation in the brain.