Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

Abstract

IntroductionEpileptic seizures are considered as a sever abnormal activity of neurons in specific areas of brain such as temporal lobe. 1 This abnormal activity of neurons can be followed by brain oxidative stress and disturbance of cognitive behaviors when they take place repeatedly. 2 In the epileptic seizure models, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase have been also shown to protect the brain of rats against oxidative damage. 3 In large number of animal studies, pentylenetetrazole (PTZ) has been repeatedly administered for induction an epilepsy model. 1 It has been ducumented that PTZstimulated seizures was accompanied with motor activity impairment, learning and memory dysfunction, axiety and increased level of hippocampal inflammatory cytokines in rats. 4 In addition, seizures followed by PTZ administration have been propounded as an important cause of oxidative status imbalance in some brain areas including hippocampus. 5 For example, PTZ infusion associated with the sever stimulation of N-Methyl-Daspartate (NMDA) receptors has been shown to elevate the level of free radicals such as nitric oxide (NO) and peroxynitrite in the brain of rats. 6 On the other hand, the antioxidant properties of angiotensin-converting enzyme (ACE) inhibitors have been accepted. 7 Captopril as a known ACE inhibitor scavenges free radicals in various tissues. 8 Captopril has been demonstrated to reinforce enzymatic and nonenzymatic defense in different tissues. 9 Scientific evidence has indicated that captopril and valsartan (a specific AT1 receptor inhibitor) attenuate A B S T R A C TBackground: Frequent seizure is followed by overproduction of free radicals and brain oxidative stress. Renin angiotensin system (RAS) has some effects on central nervous system. We designed this research to challenge the effect of captopril as an angiotensin converting enzyme (ACE) inhibitor against brain oxidative stress in pentylenetetrazole (PTZ) -induced seizures in mice. Methods: The groups were including (1) Control (saline); (2) PTZ (100 mg/kg, i.p.), (3-5) PTZ-captopril (Capto) that received three doses of Capto 10, 50 and 100 mg/kg 30 min before PTZ injection. Latency time in the onset minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) were recorded. The level of malondialdehyde (MDA) and total thiol, as well as superoxide dismutase (SOD) and catalase (CAT) activity in the hippocampus and cortex were measured. Results: All doses of captopril postponed the onset of MCS and GTCS. Accumulation of MDA in the brain tissues of PTZ group was higher than control group, while total thiol content and CAT activity were lower. Pretreatment with captopril (100 mg/kg) diminished MDA concentration compared with PTZ group. Captopril (50 and 100 mg/kg) also increased the level of total thiol groups versus PTZ group. Captopril injection (50 and 100 mg/kg) elevated the activity of SOD and CAT in the brain tissues. In addition captopril administration diminished mortality rat...