Efficacy of 8-bromoguanosine against murine cutaneous leishmaniasis induced with Leishmania amazonensis.
METHODS
In this study, we investigated the effect of 8-bromoguanosine (8Brguo), an immunostimulatory compound, in a murine model of experimental cutaneous leishmaniasis.


RESULTS
The results indicated that treatment by intraperitoneal administration of 8Brguo (150 mg/kg once daily for 1 week and thereafter once weekly for 1 month) diluted in Tween-80 produces an effect similar to that of treatment with the classical antimonial drug, Glucantime, in Leishmania amazonensis-infected CBA/J mice. While complete cure did not occur, animals treated with the nucleoside had small lesions in the infected footpad and delayed surface ulceration. Studies involving examination of serum glutamic pyruvic transaminase activity, concentration of urea, blood pathology and histology of the spleen, kidney and liver showed no apparent toxicity of the nucleoside in treated mice.


CONCLUSIONS
The protective in vivo effect during murine leishmaniasis as well as the lack of apparent toxicity of 8Brguo as attested by blood/serum pathology and histology from treated mice encourage further studies of C8-substituted guanine ribonucleosides, such as 8Brguo, as new leishmanial drugs and as modifiers of the immunological response to combat infections with intracellular pathogens.
Barão
Sandra Cristina
SC
Departamento de Parasitologia, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, Brazil.
Giorgio
Selma
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005260:Female; D006151:Guanosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006403:Hematologic Tests; D007274:Injections, Intraperitoneal; D016773:Leishmaniasis, Cutaneous / Q000097:blood / Q000188:drug therapy*; D008536:Meglumine / Q000008:administration & dosage / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D051379:Mice; D008808:Mice, Inbred CBA; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D012883:Skin Ulcer / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014508:Urea / Q000097:blood
D009942:Organometallic Compounds; D014344:Trypanocidal Agents; D006151:Guanosine; C035169:8-bromoguanosine; D008536:Meglumine; D000077485:Meglumine Antimoniate; D014508:Urea; D000410:Alanine Transaminase