Effects of fenbendazole on the murine humoral immune system.
Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the experimental use of mice until at least 6 wk after treatment should be considered.
Landin
Ana Marie
AM
Department of Microbiology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Frasca
Daniela
D
Zaias
Julia
J
Van der Put
Elaine
E
Riley
Richard L
RL
Altman
Norman H
NH
Blomberg
Bonnie B
BB
D000367:Age Factors; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000969:Antinematodal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015153:Blotting, Western / Q000662:veterinary; D024202:Electrophoretic Mobility Shift Assay / Q000662:veterinary; D017229:Enterobiasis / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D005273:Fenbendazole / Q000009:adverse effects* / Q000627:therapeutic use; D005434:Flow Cytometry / Q000662:veterinary; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012376:Rodent Diseases / Q000188:drug therapy* / Q000276:immunology
D000969:Antinematodal Agents; D051792:Basic Helix-Loop-Helix Proteins; D005273:Fenbendazole; C075668:Tcf3 protein, mouse