Vircheva Stefani, Nenkova Galina, Georgieva Almira, Alexandrova Albena, Tzvetanova Elina, Mateeva Polina, Zamfirova Rositsa, Kirkova Margarita
Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Cell Biochem Funct. 2012 Jan;30(1):18-23. doi: 10.1002/cbf.1812. Epub 2011 Sep 27.
The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG injection into the right hind paw resulted in a time-dependent increase in the paw volume; the maximum of CG-induced edema peak was in 2-4 h. A single DES dose of 20 mg · kg(-1) , administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg · kg(-1) ) suppressed the edematous response to CG. The latter drug dose protected CG-induced decrease of glutathione (non-enzyme antioxidant) in the liver; it did not affect CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of glutathione-conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS-generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries.
许多疾病和不同病理状况（包括炎症）的发病机制都与活性氧（ROS）的过量产生有关。本研究旨在探讨抗抑郁药地昔帕明（DES）对角叉菜胶（CG）诱导的炎症的影响，以及对CG注射后4小时和24小时大鼠肝脏和脾脏中细胞酶和非酶抗氧化剂内源性水平的影响。将CG足底内注射到右后爪会导致爪体积随时间增加；CG诱导的水肿峰值在2 - 4小时达到最大。在CG注射前30分钟给予20 mg·kg⁻¹的单一DES剂量，对爪水肿没有影响，而使用的较高药物剂量（50 mg·kg⁻¹）抑制了对CG的水肿反应。后一种药物剂量可保护肝脏中CG诱导的谷胱甘肽（非酶抗氧化剂）的减少；它对肝脏和脾脏中超氧化物歧化酶、谷胱甘肽过氧化物酶（酶抗氧化剂）以及葡萄糖 - 6 - 磷酸脱氢酶（对谷胱甘肽共轭抗氧化酶活性很重要的酶）的活性没有影响，这些酶的活性在CG处理后未发生变化。该药物在产生ROS的化学系统中显示出有效的抗氧化能力；它高于氟西汀（另一种抗抑郁药）。目前的结果表明，DES良好的抗氧化活性可能有助于其对肝脏损伤的有益作用。
