title: Low doses of monocrotaline in rats cause diminished bone marrow cellularity and compromised nitric oxide production by peritoneal macrophages.
abstract: Monocrotaline (MCT) is a pyrrolizidine alkaloid found in a variety of plants. The main symptoms of MCT toxicosis in livestock are related to hepato- and nephrotoxicity; in rodents and humans, the induction of a pulmonary hypertensive state that progresses to cor pulmonale has received much attention. Although studies have shown that MCT can cause effects on cellular functions that would be critical to those of lymphocytes/macrophages during a normal immune response, no immunotoxicological study on MCT have yet to ever be performed. Thus, the aim of the present study was to evaluate the effect of MCT on different branches of the immune system using the rat--which is known to be sensitive to the effects of MCT--as the model. Rats were treated once a day by gavage with 0.0, 0.3, 1.0, 3.0, or 5.0 mg MCT/kg for 14 days, and then any effects of the alkaloid on lymphoid organs, acquired immune responses, and macrophage activity were evaluated. No alterations in the relative weight of lymphoid organs were observed; however, diminished bone marrow cellularity in rats treated with the alkaloid was observed. MCT did not affect humoral or cellular immune responses. When macrophages were evaluated, treatments with MCT caused no significant alterations in phagocytic function or in hydrogen peroxide (H2O2) production; however, the MCT did cause compromised nitric oxide (NO) release by these cells.
authors.affiliation: Research Center for Veterinary Toxicology (CEPTOX), Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, S.P., Brazil.
authors.forename: Isis M
authors.initials: IM
authors.lastname: Hueza
authors.forename: Julia C
authors.initials: JC
authors.lastname: Benassi
authors.forename: Paulo C F
authors.initials: PC
authors.lastname: Raspantini
authors.forename: Leonila E R
authors.initials: LE
authors.lastname: Raspantini
authors.forename: Lilian R M
authors.initials: LR
authors.lastname: Sa
authors.forename: Silvana L
authors.initials: SL
authors.lastname: Górniak
authors.forename: Mitsue
authors.initials: M
authors.lastname: Haraguchi
mesh_terms: D000284:Administration, Oral; D000825:Animal Structures / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000473:pathology*; D002452:Cell Count; D004435:Eating / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000906:Antibodies; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D016686:Monocrotaline; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D013755:Tetradecanoylphorbol Acetate