Age-related changes in the oxidative status and antioxidant capacity in different brain regions of spontaneously hypertensive rat

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Date
2006
Authors
Tee, Chee Woui
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Abstract
Oxidant/antioxidant imbalance has been implicated in the pathogenesis of neurological disorders associated both with aging and hypertension. Therefore, we determined oxidative status and antioxidant capacity in a time-course manner in the cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Six animals from WKY and SHR strains were sacrificed at 8, 16, 24, 32, 40, 48, 56 and 64 weeks of age after measuring their blood pressure and body weight. CC, CB and BS were dissected out, homogenized and used for the following estimations: thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), total antioxidant status (TAS) and membrane-bound enzymes activities (Na+,K+-ATPase, acetylcholinesterase - AChE). SHR showed higher blood pressure and lower body weights at all time points studied. When compared to control, TBARS from week 24 and PCO from week 32 onwards increased significantly in all brain regions of SHR. GSH content and GSH/GSSG ratio were lower in SHR from weeks 16 and 24 onwards respectively in all brain regions. TAS and activities of SOD and GST were significantly decreased in all brain regions from 24 weeks onwards in SHR. GPx activity showed significant decrease in CB and BS from week 24 and CC from week 56 onwards in SHR. CAT activity was significantly lower in CB from week 32 and CC from week 56 onwards in SHR. There was no difference in CAT activity in BS at all time points studied. GR activity showed significant decrease in CC, CB and BS from weeks 48, 16 and 24 onwards respectively in SHR. Na+,K+-ATPase showed significant decrease in its activity from week 32 onwards in all brain regions of SHR. AChE activity was significantly lower in CC, CB and BS from weeks 24, 32 and 48 onwards respectively in SHR. All three brain regions had similar SOD activity. BS of WKY and SHR had significantly higher TAS, activities of CAT and GPx, and lower TBARS and PCO levels in comparison to CC. Similar PCO levels and GPx activity were found in CB and BS, but significantly higher TAS and CAT activity, and lower TBARS levels were found in BS compared to CB. However, GSH contents, GSH/GSSG ratio and activities of GST and GR were significantly lower in BS compared to CC and CB. CC and CB had similar TBARS and PCO levels, GSH contents and TAS, but activities of GPx, CAT and GR were significantly lower in CC compared to CB. It is suggested that the brain regions toward oxidative stress is in the order: CC>CB>BS. Along with progression of hypertension, there is increased oxidants level and decreased antioxidants capacity with alteration in membrane-bound enzymes activities in CC, CB and BS of SHR. Thus, oxidative stress may play a role in hypertension-associated neurological diseases.
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Master
Keywords
Biological Science , Antioxidant capacity , Brain regions , Hypertensive rat
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