title: Potential role of licofelone, minocycline and their combination against chronic fatigue stress induced behavioral, biochemical and mitochondrial alterations in mice.
abstract: BACKGROUND
  Chronic fatigue stress (CFS) is a common complaint among general population. Persistent and debilitating fatigue severely impairs daily functioning and is usually accompanied by combination of several physical and psychiatric problems. It is now well established fact that oxidative stress and neuroinflammation are involved in the pathophysiology of chronic fatigue and related disorders. Targeting both COX (cyclooxygenase) and 5-LOX (lipoxygenase) pathways have been proposed to be involved in neuroprotective effect.
  
  
  METHODS
  In the present study, mice were put on the running wheel apparatus for 6 min test session daily for 21 days, what produced fatigue like condition. The locomotor activity and anxiety like behavior were measured on 0, 8(th), 15(th) and 22(nd) day. The brains were isolated on 22(nd) day immediately after the behavioral assessments for the estimation of oxidative stress parameters and mitochondrial enzyme complexes activity.
  
  
  RESULTS
  Pre-treatment with licofelone (2.5, 5 and 10 mg/kg, po) and minocycline (50 and 100 mg/kg, po) for 21 days, significantly attenuated fatigue like behavior as compared to the control (rotating wheel activity test session, RWATS) group. Further, licofelone (5 and 10 mg/kg, po) and minocycline (50 and 100 mg/kg, po) drug treatments for 21 days significantly attenuated behavioral alterations, oxidative damage and restored mitochondrial enzyme complex activities (I, II, III and IV) as compared to control, whereas combination of licofelone (5 mg/kg) with minocycline (50 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect per se.
  
  
  CONCLUSIONS
  The present study highlights the therapeutic potential of licofelone, minocycline and their combination against CFS in mice.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh-160014, India. kumaruips@yahoo.com
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Aditi
authors.initials: A
authors.lastname: Vashist
authors.forename: Puneet
authors.initials: P
authors.lastname: Kumar
authors.forename: Harikesh
authors.initials: H
authors.lastname: Kalonia
authors.forename: Jitendriya
authors.initials: J
authors.lastname: Mishra
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000378:metabolism / Q000523:psychology*; D005978:Glutathione / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008911:Minocycline / Q000008:administration & dosage / Q000627:therapeutic use*; D008928:Mitochondria / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D011758:Pyrroles; D008911:Minocycline; D005978:Glutathione; C088092:licofelone