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Published on: July 31, 2017
Oxidative stress in prefrontal cortex of rat exposed to MK-801 and protective effects of CAPE
Birsen Ozyurt1, Huseyin Ozyurt, Nusret Akpolat
1Gaziosmanpasa University Faculty of Medicine, Department of Anatomy, Dekanlik Binasi, Tokat, Turkey. mdbirsen@hotmail.com
Abstract:
MK-801 was shown to be one of the most neurotoxic non-competitive NMDA receptor antagonists. It is known that repeated injection of MK-801 was proposed in an animal model in psychosis. The aims of this study are to investigate the contributing effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Furthermore, there is evidence that oxygen free radicals play an important role in the pathophysiology of schizophrenia. In this study, Wistar Albino rats were divided into three groups: 1st group: Control, 2nd group: MK-801, 3rd group: MK-801+CAPE (Caffeic acid phenethyl ester) group. MK-801 was given intraperitoneally at the dose of 0.5 mg/kg/day for 5 days. CAPE was given to the treatment group while exposed to MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal cortex (PFC) of rats was removed for biochemical and histological analyses. As a result, malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) and adenosine deaminase (AD) enzyme activities were found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (p<0.0001) compared to control group. In CAPE treated rats, prefrontal tissue MDA, PC, NO levels and, GSH-Px, XO, AD enzyme activities were significantly decreased when compared to MK-801 groups (p<0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. CAPE treatment decreased the apoptotic cell count in PFC. The results of this study showed that MK-801-induced neurotoxicity caused oxidative stress in PFC of rats. This experimental study may also provide some evidences for the new treatment strategies with antioxidants in schizophrenia.
Insights
MK-801 induced experimental psychosis and neurotoxicity, increasing oxidative stress in rat prefrontal cortex. Caffeic acid phenethyl ester (CAPE) treatment reduced oxidative stress markers and apoptosis, suggesting antioxidant potential for schizophrenia treatment.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- MK-801 is a neurotoxic NMDA receptor antagonist used in experimental psychosis models.
- Oxidative stress and free radicals are implicated in the pathophysiology of schizophrenia.
Purpose of the Study:
- To investigate the role of oxidative stress in MK-801-induced experimental psychosis.
- To evaluate if preventing oxidative stress with Caffeic acid phenethyl ester (CAPE) improves outcomes.
Main Methods:
- Wistar rats received MK-801 (0.5 mg/kg/day for 5 days) or saline.
- One group received MK-801 concurrently with CAPE.
- Prefrontal cortex tissue was analyzed for oxidative stress markers and enzyme activities.
Main Results:
- MK-801 significantly increased oxidative stress markers (MDA, PC, NO) and enzyme activities (SOD, GSH-Px, XO, AD) in the prefrontal cortex.
- CAPE treatment significantly reduced these markers and enzyme activities, except for catalase (CAT).
- MK-801 induced apoptosis, which was reduced by CAPE treatment.
Conclusions:
- MK-801-induced neurotoxicity in rats is associated with significant oxidative stress in the prefrontal cortex.
- CAPE demonstrates potential as an antioxidant therapy, mitigating MK-801-induced oxidative stress and apoptosis.
- These findings support exploring antioxidant strategies for treating schizophrenia.
