Protective effect of desipramine, venlafaxine and trazodone against experimental animal model of transient global ischemia: possible involvement of NO-cGMP pathway.
The present study has been designed to explore the nitric oxide mechanism in the protective effect of desipramine, venlafaxine and trazodone against I/R induced oxidative stress and mitochondrial dysfunction in mice. Vitamin E was taken as standard antioxidant. Laca mice (25-30 g) were subjected to twice BCCAO occlusion (5 min) at the interval of 10 min, followed by 96 h reperfusion. The drug treatments were started from the day of surgery and continued for the next four days. After 96 h the animals were sacrificed for biochemical (malondialdehyde, nitrite concentration, superoxidedismutase, catalase, redox ratio and GST) and mitochondrial enzyme complex (NADH dehydrogenase, succinate dehydrogenase, MTT assay and cytochrome c oxidase) estimations. Ischemia caused significant oxidative damage and mitochondrial enzyme dysfunction after 96 h of reperfusion as compared to sham operated animals. Antidepressant (desipramine, venlafaxine and trazodone) treatment significantly attenuated oxidative damage and restored mitochondrial enzyme complex activities as compared to control (I/R) group. Further, protective effects of desipramine (15 mg/kg) and/or venlafaxine (5 mg/kg) were attenuated by l-arginine (100 mg/kg) or sildenafil (5 mg/kg) pretreatment. Further, L-NAME (10 mg/kg) or 7-NI (10 mg/kg) pretreatment with desipramine (15 mg/kg) and/or venlafaxine (5 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone. The present study highlights the involvement of nitric oxide mechanism in the protective effects of desipramine and venlafaxine against I/R induced oxidative stress and mitochondrial dysfunction in mice.
Gaur
Vaibhav
V
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160014, India.
Kumar
Anil
A
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003511:Cyclohexanols / Q000627:therapeutic use; D003891:Desipramine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014196:Trazodone / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D003511:Cyclohexanols; D045222:Electron Transport Chain Complex Proteins; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D000069470:Venlafaxine Hydrochloride; D001120:Arginine; D002374:Catalase; D005978:Glutathione; D006152:Cyclic GMP; D003891:Desipramine; D014196:Trazodone