PMID- 23454832 OWN - NLM STAT- MEDLINE DCOM- 20130614 LR - 20161125 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 219 IP - 2 DP - 2013 May 23 TI - The suppression of hematopoiesis function in Balb/c mice induced by prolonged exposure of microcystin-LR. PG - 194-201 LID - S0378-4274(13)00080-5 [pii] LID - 10.1016/j.toxlet.2013.02.011 [doi] AB - 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 mug/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 mug/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 mug/kg bw groups. Serum levels of some hematopoietic growth factors significantly changed in 8 mug/kg bw group, mainly including granulocyte-macrophage (GM-CSF), erythropoietin (EPO), interleukin-3 (IL-3) and TNF-alpha. The transcriptional levels of these 4 genes in BMCs were also significantly changed in 8 mug/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. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Zhou, Wenshan AU - Zhou W AD - Fisheries College of Huazhong Agricultural University, Wuhan 430070, People's Republic of China. zhouwenshan@webmail.hzau.edu.cn FAU - Zhang, Xuezhen AU - Zhang X FAU - Xie, Ping AU - Xie P FAU - Liang, Hualei AU - Liang H FAU - Zhang, Xin AU - Zhang X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130227 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Hematopoietic Cell Growth Factors) RN - 0 (Marine Toxins) RN - 0 (Microcystins) RN - 63231-63-0 (RNA) RN - EQ8332842Y (cyanoginosin LR) SB - IM MH - Anemia/blood/chemically induced MH - Animals MH - Apoptosis/drug effects MH - Blood Cell Count MH - Bone Marrow Cells/drug effects MH - Cell Proliferation/drug effects MH - Enzyme-Linked Immunosorbent Assay MH - Erythrocyte Indices MH - Flow Cytometry MH - Hematopoiesis/*drug effects MH - Hematopoietic Cell Growth Factors/blood MH - Male MH - Marine Toxins/*toxicity MH - Mice MH - Mice, Inbred BALB C MH - Microcystins/*toxicity MH - Micronucleus Tests MH - RNA/biosynthesis/isolation & purification MH - Real-Time Polymerase Chain Reaction EDAT- 2013/03/05 06:00 MHDA- 2013/06/15 06:00 CRDT- 2013/03/05 06:00 PHST- 2012/10/27 00:00 [received] PHST- 2013/02/18 00:00 [revised] PHST- 2013/02/19 00:00 [accepted] PHST- 2013/03/05 06:00 [entrez] PHST- 2013/03/05 06:00 [pubmed] PHST- 2013/06/15 06:00 [medline] AID - S0378-4274(13)00080-5 [pii] AID - 10.1016/j.toxlet.2013.02.011 [doi] PST - ppublish SO - Toxicol Lett. 2013 May 23;219(2):194-201. doi: 10.1016/j.toxlet.2013.02.011. Epub 2013 Feb 27.