Acta Vet. Brno 2009, 78: 483-490

Influence of Midazolam and L-Arginine on Clinical Observations and Biochemical Changes in Rat Liver Induced by Pentylenetetrazole

Ankica Jelenkovic1, D. Marina Jovanovic2, Dragan Đurđević2, Danica Stanimirovic3, Dubravko Bokonjić2, Ivana Vasiljevic2, Rosa Mihajlovic4

1Institute for Biological Research Sinisa Stankovic, University of Belgrade, Serbia
2Military Medical Academy, Institute for Medical Research, Belgrade, Serbia
3Institute for Biological Sciences, National Research Council, Ottawa, Canada
4Institute for Rehabilitation, Belgrade, Serbia

Received December 18, 2008
Accepted March 9, 2009

Certain types of convulsions may lead to multiorgan dysfunction. We investigated whether the chemoconvulsant pentylenetetrazole (PTZ) could influence energy synthesis in the liver besides evoking convulsions in adult male Wistar rats. In 80% of the rats PTZ (100 mg/kg body weight, administered intraperitoneally – i.p.) evoked generalised clonic convulsions (GCCs) and in 60% of the rats generalised clonic-tonic convulsions (GCTCs) within 4 min after its administration. Cytochrome c oxidase activity was simultaneously reduced approximately three-fold compared to 0.9% NaCl-treated (control) rats (p < 0.01). Midazolam administered before PTZ was an excellent anti-convulsant especially against GCCs (p < 0.05). However, it did not protect against the decrease in cytochrome c oxidase activity induced by PTZ. In contrast to midazolam, pretreatment with L-arginine did not prevent PTZ-evoked convulsions. However, it offered some protection against the PTZ-mediated reduction in cytochrome c oxidase activity. Our results open new avenues of research that will focus on the mechanisms of action of PTZ, midazolam and L-arginine with particular reference to their direct and/or indirect effects on liver function.