| Popis: |
Prajmaline, a useful drug to treat cardiac arrhythmias can occasionally be associated with hepatic toxicity. To study the mechanism of prajmaline toxicity, its effect on the hepatic glutathione system was investigated. Two groups of male Sprague-Dawley rats (200–300 g body weight) were used: 12 rats were treated with a daily i.p. dose of 1.5 mg prajmalium bitartrate for 3 days; the 12 controls received the vehicle i.p. On the third day the rats were sacrificed and the following parameters were determined in the liver homogenate: reduced glutathione (GSH) using the glyoxalase assay, GSH-S-transferase (GSH-T) using 1-chloro 2,4 dinitrobenzene, GSH-peroxidase (GSHPx) using t-butylhydroperoxide, GSSG-reductase and the activities of two NADPH regenerating enzymes [glucose 6-phosphate (GDH) and isocitrate dehydrogenase (IDH)]. With prajmaline the hepatic GSH content and the activity of the GSH-Px were significantly depressed (GSH: 4.3 ± 1.0 versus 5.2 ± 0.7 µmol/g liver wet weight; GSH-Px: 160 ± 31 versus 190 ± 39 nmol/ min/10 mg wet weight \(\bar x \pm SD\) ). The GSSG-reductase and the GSH-T activities were unchanged. However, the IDH activity was also reduced (416±50 versus 453 ± 63 nmol/min/10 mg wet weight) with prajmaline treatment. |
