Abstract
Background: Oxidative damage contributes to the pathophysiology of schizophrenia (SZ). Redox imbalance may lead to increased lipid peroxidation, which produces toxic aldehydes like 4-hydroxynonenal (4-HNE) ultimately leading to oxidative stress. Conversely, implications of oxidative stress point towards an alteration in HNE-protein adducts and activities of enzymatic and antioxidant systems in schizophrenia.
Objectives: The present study focuses on the identification of HNE-protein adducts and their related molecular consequences in schizophrenia pathology due to oxidative stress, particularly lipid peroxidation.
Materials and Methods: Oxyblotting was performed on seven autopsied brain samples each from the cortex and hippocampus region of schizophrenia patients and their respective normal healthy controls. Additionally, Thiobarbituric Acid Substances (TBARS), reduced Glutathione (GSH) levels and catalase (CAT) activities associated with oxidative stress, were also estimated.
Results: Obtained results indicate substantially higher levels of oxidative stress in schizophrenia patients than healthy control group represented by elevated expression of HNE-protein adducts. Interestingly, the hippocampus region of schizophrenia brain shows increased HNE protein adducts compared to cortex. An increase in catalase activity (4.8876±1.7123) whereas a decrease in antioxidant GSH levels (0.213±0.015μmol/ml) have been observed in SZ brain. Elevated TBARS levels (0.3801±0.0532ug/ml) were obtained in brain regions of SZ patients compared with their controls that reflect increased lipid peroxidation (LPO).
Conclusion: We propose the role of HNE modified proteins possibly associated with the pathology of schizophrenia. Our data revealed increased lipid peroxidation as a consequence of increased TBARS production. Furthermore, altered cellular antioxidants pathways related to GSH and CAT also highlight the involvement of oxidative stress in schizophrenia pathology.
Keywords: Lipid peroxidation, polyunsaturated fatty acid, reduced glutathione, 4-hydroxynonenal, malondialdehyde, thiobarbituric acid reactive substances, catalase.
Graphical Abstract
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