title: 3,3'-Diindolylmethane induces immunotoxicity via splenocyte apoptosis in neonatal mice.
abstract: 3,3'-Diindolylmethane (DIM), a major product of indole-3-carbinol derived from vegetables of the genus Brassica, exhibits chemotherapeutic activity and various immune modulatory effects in animal models and in vitro studies. Although extensive studies have only focused on DIM's beneficial effects, the toxic effects of DIM on the immune systems have not been clearly elucidated. The aim of this study was to explore the immunotoxic effects of DIM in a neonatal mouse and to further evaluate whether DIM administration affects rotavirus (RV)-induced gastroenteritis. Interestingly, multiple immunotoxic effects were observed in the DIM treated group, including decreases in various immune cells (F4/80(+), CD11c(+), CD19(+), and CD3(+) cells) in the spleen, induction of splenic white pulp atrophy, an increase in immune cell apoptosis, and decreased expression of various toll-like receptors (TLRs) in the spleen and small intestine. Apoptosis was notably promoted by up-regulating caspase-3 activity and by the change in the ratio of Bcl-2/Bax activities. Finally, oral administration of DIM led to deterioration of RV-induced intestinal disease and delayed viral clearance in the intestine and MLNs. Our results indicate that oral administration of DIM in neonatal mice induces immunotoxicity and hampers efficient RV clearance in the intestine. This new information about the immunotoxic roles of DIM in a newborn mouse model may provide valuable clues for the development of a safe supplement, especially one designed for human infants.
authors.affiliation: Biosafety Research Institute and Department of Pathology, College of Veterinary Medicine, Chonbuk National University, Jeonju, South Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Roh
authors.forename: Ara
authors.initials: A
authors.lastname: Cho
authors.forename: Mohammad Rafiqul
authors.initials: MR
authors.lastname: Islam
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Jinho
authors.initials: J
authors.lastname: Kim
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: John Wha
authors.initials: JW
authors.lastname: Lee
authors.forename: Chae Woong
authors.initials: CW
authors.lastname: Lim
authors.forename: Bumseok
authors.initials: B
authors.lastname: Kim
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005759:Gastroenteritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects*; D007211:Indoles / Q000008:administration & dosage / Q000633:toxicity*; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012400:Rotavirus Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D007211:Indoles; D012333:RNA, Messenger; D051193:Toll-Like Receptors; C016392:3,3'-diindolylmethane