title: The suppression of hematopoiesis function in Balb/c mice induced by prolonged exposure of microcystin-LR.
abstract: Microcystins (MCs) cause normocytic anemia in patients in a hemodialysis unit in Caruaru, Brazil in 1996, but the underlying mechanisms are still unclear. In the present study, Balb/c mice were intraperitoneally injected with microcystin-LR (MC-LR) at the doses of 0.5, 2 and 8 μg/kg body weight (bw) every 48 h for 30 d. After the prolonged exposure of MC-LR, significant decreases of red blood cell count (RBC), hemoglobin (Hb) and hematocrit (Ht) were observed in 2 and 8 μg/kg bw groups, but erythrocyte mean corpuscular volume (MCV) showed no significant changes. Significantly elevated micronucleus frequency was observed in bone marrow cells (BMCs) in all MC-LR treatments. The proliferation of BMCs significantly declined in both 2 and 8 μg/kg bw groups. Serum levels of some hematopoietic growth factors significantly changed in 8 μg/kg bw group, mainly including granulocyte-macrophage (GM-CSF), erythropoietin (EPO), interleukin-3 (IL-3) and TNF-α. The transcriptional levels of these 4 genes in BMCs were also significantly changed in 8 μg/kg bw group. MC-LR exposure significantly increased the apoptosis rates in all MC-LR treatments. The present study indicates prolonged exposure of MC-LR induces normocytic anemia, and the disturbed hematopoietic growth factors and BMCs apoptosis are responsible for this normocytic anemia.
authors: Fisheries College of Huazhong Agricultural University, Wuhan 430070, People's Republic of China. zhouwenshan@webmail.hzau.edu.cn
authors: Wenshan
authors: W
authors: Zhou
authors: Xuezhen
authors: X
authors: Zhang
authors: Ping
authors: P
authors: Xie
authors: Hualei
authors: H
authors: Liang
authors: Xin
authors: X
authors: Zhang
mesh_terms: D000740:Anemia / Q000097:blood / Q000139:chemically induced; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004909:Erythrocyte Indices; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000097:blood; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D052998:Microcystins / Q000633:toxicity*; D015162:Micronucleus Tests; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016298:Hematopoietic Cell Growth Factors; D008387:Marine Toxins; D052998:Microcystins; D012313:RNA; C057862:cyanoginosin LR