Treatment with benznidazole in association with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi: investigation into the possible development of neoplasias.
Benznidazole is recommended in Brazil for the treatment of Trypanosoma cruzi infection in acute and early chronic phases of Chagas' disease. Observations by others have indicated a higher incidence of neoplasias in immunosuppressed patients, presenting Chagas' disease reactivation, submitted to treatment with benznidazole. In the present study, we investigated whether there is a potentiation in the generation of lymphomas in chronically infected mice, treated with immunosuppressive drugs and benznidazole. For this, 142 Swiss mice chronically infected with the 21 SF strain of T. cruzi and 72 normal Swiss mice were used. Both infected and normal mice were divided into experimental groups and submitted to one of the following treatment regimens: benznidazole alone; immunosuppressive drugs (azathioprine, betamethasone and cyclosporin); a combination of immunosuppressive drugs and benznidazole; and untreated controls. In the infected group treated with benznidazole, one mouse developed a non-Hodgkin's lymphoma. This finding has been interpreted as a spontaneous tumor of mice. The study of the chronically infected mice treated with the combination of immunosuppressive drugs and benznidazole demonstrated an absence of lymphomas or other neoplasias. These findings support the indication of benznidazole, as the drug of choice, for immunosuppressed patients that develop a reactivation of Chagas' disease.
Andrade
Sonia G
SG
Laboratório de Doença de Chagas Experimental, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brasil.
Mesquita
Igor Marcelo Oliveira
IM
Jambeiro
Jamile F
JF
Santos
Isis F Magalhães
IF
Portella
Renata Siqueira
RS
D000818:Animals; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D001623:Betamethasone / Q000009:adverse effects / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy* / Q000473:pathology; D002908:Chronic Disease; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D004338:Drug Combinations; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007958:Leukocyte Count; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D009593:Nitroimidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000009:adverse effects* / Q000627:therapeutic use
D004338:Drug Combinations; D007166:Immunosuppressive Agents; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D016572:Cyclosporine; D001623:Betamethasone; D001379:Azathioprine; C009999:benzonidazole