Objectives:

Previous studies have shown that gene expressions can be regulated in the hippocampus of rats after seizures induced by kainic acid (KA). The purpose of this study was to examine the potential regulatory impact of KA administration on gene expression levels of enzymes responsible for drug metabolism in the rat hippocampal tissue.

Materials and Methods:

Rats received intraperitoneal injections of KA and saline at a dose of 10 mg/kg each. Behavioral changes were observed in experimental animals following the administration of KA. Four hours after receiving treatments, all rats were decapitated, and the brains were removed. Hippocampal tissues were used for total RNA isolation, and cDNA synthesis was achieved by reverse transcription PCR. Gene expression levels of enzymes responsible for drug metabolism were determined by qPCR using the RT2 Profiler PCR Array Rat Drug Metabolism PCR array system containing the relevant primers for a total of 84 genes. The gene expression levels of drug-metabolising enzymes (DMEs) were quantified using comparative Ct (2-ΔΔCt) method. Student's t-test was used for data analysis.

Results:

Our results indicate that KA treatment caused significant changes in the gene expression levels of metallothionein 3 (Mt3), glucose phosphate isomerase (Gpi), ATP-binding cassette protein C1 (Abcc1), cytochrome P450 enzymes (Cyp2c6v1, Cyp3a23/3a1, Cyp2c7), glutathione peroxidase 1, 4 and 5 (Gpx1, Gpx4, Gpx5), glutamic acid decarboxylase 1 and 2 (Gad1, Gad2), paraoxonase 2 (Pon2), carbohydrate sulfotransferase 1 (Chst1), glutathione S-transferases (Gsta3, Gstm1, Gstm4), microsomal glutathione S-transferase 3 (Mgst3), carboxylesterase 2C (Ces2c), fatty acid amide hydrolase (Faah), pyruvate kinase-muscle (Pkm2), arachidonate 5- lipoxygenase (Alox5), apolipoprotein E (Apoe), cytochrome b5 reductase 5 (Cyb5r5), xanthine dehydrogenase (Xdh), N-acetyltransferase 1 (Nat1), glucokinase regulator (Gckr), hexokinase 2 (Hk2), myristoylated alanine rich protein kinase C substrate (Marcks), and stannin (Snn) in hippocampus compared to control (p<0.05).

Conclusion:

As a conclusion, it can be said that the seizure activity triggered by KA has the potential to change the gene expression levels of the enzymes responsible for drug metabolism in the hippocampus of rats.

Keywords: Kainic acid, status epilepticus, hippocampus, drug metabolism, gene expression, PCR array