Oxidative stress parameters in unmediated and treated bipolar subjects during initial manic episode: A possible role for lithium antioxidant effects

Institute of Psychiatry, University of São Paulo, San Paulo, São Paulo, Brazil
Neuroscience Letters (Impact Factor: 2.03). 07/2007; 421(1):33-6. DOI: 10.1016/j.neulet.2007.05.016
Source: PubMed


Studies have proposed the involvement of oxidative stress and neuronal energy dysfunctions in the pathophysiology of bipolar disorder (BD). This study evaluates plasma levels of the oxidative/energy metabolism markers, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and neuron-specific enolase (NSE) during initial episodes of mania compared to controls in 75 subjects. Two groups of manic subjects (unmedicated n=30, and lithium-treated n=15) were age/gender matched with healthy controls (n=30). TBARS and antioxidant enzymes activity (SOD and CAT) were increased in unmedicated manic patients compared to controls. Conversely, plasma NSE levels were lower during mania than in the controls. In contrast, acute treatment with lithium showed a significant reduction in both SOD/CAT ratio and TBARS levels. These results suggest that initial manic episodes are associated with both increased oxidative stress parameters and activated antioxidant defenses, which may be related to dysfunctions on energy metabolism and neuroplasticity pathways. Antioxidant effects using lithium in mania were shown, and further studies are necessary to evaluate the potential role of these effects in the pathophysiology and therapeutics of BD.

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Available from: Rodrigo Machado-Vieira, May 13, 2014
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    • "disorder (BD) (Clay et al. 2011; Machado-Vieira et al. 2013). Previous studies reported increased oxidative stress in postmortem brains and peripheral blood samples of BD subjects (Andreazza et al. 2008, 2010; Machado-Vieira et al. 2007), suggesting energy dysfunction at mitochondrial electron transport chain (ETC) complexes. A decrease in mitochondrial ETC complex I activity was observed in postmortem BD, associated with elevated oxidative stress parameters (Andreazza et al. 2010). "
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    ABSTRACT: Different lines of evidence suggest that mitochondrial dysfunction may be implicated in bipolar disorder (BD) pathophysiology. Mitochondrial electron transport chain (ETC) is a key target to evaluate mitochondrial function, but its activity has never been assessed in unmedicated BD or during mood episodes. Also, lithium has been shown to increase ETC gene expression/activity in preclinical models and in postmortem brains of BD subjects, but to date, no study has evaluated lithium's direct effects on ETC activity in vivo.
    Full-text · Article · Jun 2014 · Psychopharmacology
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    • "Catalase and glutathione peroxidase levels are also elevated in patients with bipolar disorder during depressive episodes [32]. Treatment with the mood-stabilizer lithium reduces thiobarbituric acid reactive substances in those patients presenting for an initial manic episode as well as in those patients with episodes of hypomania (bipolar disorder type II) [32, 33]. Lithium administration in bipolar disorder patients has been noted to increase the activity of the Na+ K+ ATPase, a cellular event which is independently associated with reduction in lipid peroxidation [34]. "
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    ABSTRACT: The brain is known to be sensitive to oxidative stress and lipid peroxidation. While lipid peroxidation has been shown to contribute to many disease processes, its role in psychiatric illness has not been investigated until recently. In this paper, we provide an overview of lipid peroxidation in the central nervous system as well as clinical data supporting a link between lipid peroxidation and disorders such as schizophrenia, bipolar disorder, and major depressive disorder. These data support further investigation of lipid peroxidation in the effort to uncover therapeutic targets and biomarkers of psychiatric disease.
    Full-text · Article · Apr 2014 · Oxidative medicine and cellular longevity
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    • "Studies revealed that among other things, lithium toxicity can be connected with oxidative stress [6, 10, 13, 36], but contradicting outcomes were also reported [39, 40]. Furthermore, oxidative stress was also found to be involved into the pathophysiology of bipolar disorder [40, 41]. As long-term lithium therapy is used in the cure of this disease, the question of the influence of lithium on oxidative processes is an issue of great importance. "
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    ABSTRACT: Lithium is widely used in medicine, but its administration can cause numerous side effects. The present study aimed at the evaluation of the possible application of selenium, an essential and antioxidant element, as a protective agent against lithium toxicity. The experiment was performed on four groups of Wistar rats: I (control)-treated with saline, II (Li)-treated with lithium (Li2CO3), III (Se)-treated with selenium (Na2SeO3) and IV (Li + Se)-treated with lithium and selenium (Li2CO3 and Na2SeO3) in the form of water solutions by stomach tube for 6 weeks. The following biochemical parameters were measured: concentrations of sodium, potassium, calcium, magnesium, phosphorus, iron, urea, creatinine, cholesterol, glucose, total protein and albumin and activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in serum as well as whole blood superoxide dismutase and glutathione peroxidase. Morphological parameters such as red blood cells, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets, white blood cells, neutrophils as well as lymphocytes were determined. Lithium significantly increased serum calcium and glucose (2.65 ± 0.17 vs. 2.43 ± 0.11; 162 ± 31 vs. 121 ± 14, respectively), whereas magnesium and albumin were decreased (1.05 ± 0.08 vs. 1.21 ± 0.15; 3.85. ± 0.12 vs. 4.02 ± 0.08, respectively). Selenium given with lithium restored these parameters to values similar to those observed in the control (Ca-2.49 ± 0.08, glucose-113 ± 26, Mg-1.28 ± 0.09, albumin-4.07 ± 0.11). Se alone or co-administered with Li significantly increased aspartate aminotransferase and glutathione peroxidase. The obtained outcomes let us suggest that the continuation of research on the application of selenium as an adjuvant in lithium therapy seems warranted.
    Full-text · Article · Mar 2014 · Biological trace element research
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