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: Wenshan Zhou, Xuezhen Zhang, Ping Xie, Hualei Liang, Xin Zhang
• Journal: Toxicology letters (Toxicol Lett) Vol. 219 Issue 2 Pg. 194-201 (May 23 2013) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 23454832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Hematopoietic Cell Growth Factors
• Marine Toxins
• Microcystins
• RNA
• cyanoginosin LR

Topics

• Anemia (blood, chemically induced)
• Animals
• Apoptosis (drug effects)
• Blood Cell Count
• Bone Marrow Cells (drug effects)
• Cell Proliferation (drug effects)
• Enzyme-Linked Immunosorbent Assay
• Erythrocyte Indices
• Flow Cytometry
• Hematopoiesis (drug effects)
• Hematopoietic Cell Growth Factors (blood)
• Male
• Marine Toxins (toxicity)
• Mice
• Mice, Inbred BALB C
• Microcystins (toxicity)
• Micronucleus Tests
• RNA (biosynthesis, isolation & purification)
• Real-Time Polymerase Chain Reaction