Targeting cyclooxygenase-2 in depression is not a viable therapeutic approach and may even aggravate the pathophysiology underpinning depression

被引:49
作者
Maes, Michael [1 ]
机构
[1] Piyavate Hosp, Maes Clin TRIA, Bangkok 10310, Thailand
关键词
Depression; Cytokines; Inflammation; COX-2; Cardiovascular disorder; Leaky gut; Oxidative and nitrosative stress; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NITROSATIVE STRESS PATHWAYS; RANDOMIZED CONTROLLED-TRIAL; INFLAMMATORY-BOWEL-DISEASE; MEDIATED IMMUNE ACTIVATION; MAJOR DEPRESSION; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; COX-2; INHIBITION; GASTROINTESTINAL TOXICITY;
D O I
10.1007/s11011-012-9326-6
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Depression is a complex progressive disorder accompanied by activation of inflammatory and Th-1 driven pathways, oxidative and nitrosative stress (O&NS), lowered antioxidant levels, mitochondrial dysfunctions, neuroprogression and increased bacterial translocation. In depression, activation of immuno-inflammatory pathways is associated with an increased risk for cardio-vascular disorder (CVD). Because of the inflammatory component, the use of cyclooxygenase 2 (COX-2) inhibitors, such as celecoxib, has been advocated to treat depression. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this selective review on the effects of COX-2 inhibitors aggravating the abovementioned pathways. COX-2 inhibitors may induce neuroinflammation, exacerbate Th1 driven responses, increase lipid peroxidation, decrease the levels of key antioxidants, damage mitochondria and aggravate neuroprogression. COX-2 inhibitors may aggravate bacterial translocation and CVD through Th1-driven mechanisms. COX-2 inhibitors may aggravate the pathophysiology of depression. Since Th1 and O&NS pathways are risk factors for CVD, the use of COX-2 inhibitors may further aggravate the increased risk for CVD in depression. Selectively targeting COX-2 may not be a viable therapeutic approach to treat depression. Multi-targeting of the different pathways that play a role in depression is more likely to yield good treatment results.
引用
收藏
页码:405 / 413
页数:9
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