Therapeutic effects of combined treatment with ribavirin and tiazofurin on experimental autoimmune encephalomyelitis development: clinical and histopathological evaluation.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and the helpful tool in preclinical testing of various substances considered for treatment of this human CNS disease. Ribavirin (R) and tiazofurin (T) are purine nucleoside analogues, with the broad spectrum of anti-viral, anti-tumoral and anti-inflammatory properties. We proposed that combined treatment with RT, administrated during the effector phase of EAE, would attenuate disease severity, both clinically and pathologically. Ribavirin was given daily at a dosage of 30 mg/kg and tiazofurin was given at a dosage of 10 mg/kg every other day for 15 days. We detected amelioration of clinical signs and faster recovery in the RT group compared to the control group. Immunohistochemical analyses revealed that RT treatment decrease the number of T cells, macrophages and microglia. In the controls, we detected reactive type of microglia, while in the RT group we noticed ramified/resting form. Demyelination areas and axonal damage were not recorded in the RT group, in contrast to the control group where multiple areas of demyelination zones and axonal loss were found. RT combination treatment suppresses ongoing EAE, prevents demyelination and axonal loss, and therefore may well be the potential therapy for the treatment of MS.
Stojkov
Danijela
D
Department of Neurobiology, Institute for Biological Research Sinisa Stankovic, Bulevar Despota Stefana 142, Belgrade, 11000, Serbia. danisto@ibiss.bg.ac.yu
Lavrnja
Irena
I
Pekovic
Sanja
S
Dacic
Sanja
S
Bjelobaba
Ivana
I
Mostarica-Stojkovic
Marija
M
Stosic-Grujicic
Stanislava
S
Jovanovic
Sasa
S
Nedeljkovic
Nadezda
N
Rakic
Ljubisav
L
Stojiljkovic
Mirjana
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005911:Gliosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051381:Rats; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology
D000964:Antimetabolites, Antineoplastic; D000998:Antiviral Agents; D012254:Ribavirin; C033706:tiazofurin