Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder

Objectives: Oxidative stress induced lipid peroxidation along with a reduced Na+-K+-ATPase activity has been implicated in the pathophysiology of bipolar disorders (BPD). Although, lithium therapy results in significant improvement in the symptoms of the disease, studies regarding its effect on the altered sodium pump activity and lipid peroxidation status have come out with conflicting results. The present study was undertaken to evaluate the status of lipid peroxidation and analyze the role of lithium and Na+-K+-ATPase activity in its regulation in BPD patients in our region. Method: We measured RBC membrane Na+-K+-ATPase activity and serum thiobarbituric acid reacting substances (TBARS) level in 73 BPD patients and serum lithium, in addition, in 48 patients receiving lithium therapy among them. Results: Na+-K+-ATPase activity and serum TBARS level were significantly decreased and increased respectively in all BPD patients compared to age and sex matched healthy controls. Same trend was observed in the BPD patients stabilized on lithium therapy compared to the lithium naive ones. Although, the enzyme activity showed a reciprocal relationship with TBARS in all patients of BPD, a significant positive correlation and dependence of the enzyme activity was evident with serum lithium level only in the lithium stabilized BPD group. Conclusions: BPD patients showed significantly compromised Na+-K+-ATPase activity and increased lipid peroxidation. Lithium induced improvement in the enzyme activity was associated with significant reduction in lipid peroxidation. Enhancement of the Na+-K+-ATPase activity by optimum dosage of lithium may be a potential contributing factor for reducing oxidative stress in BPD patients. (c) 2011 Elsevier Inc. All rights reserved.