cyanoginosin-lr and Anemia

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.

Topics: Anemia; Animals; Apoptosis; Blood Cell Count; Bone Marrow Cells; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Erythrocyte Indices; Flow Cytometry; Hematopoiesis; Hematopoietic Cell Growth Factors; Male; Marine Toxins; Mice; Mice, Inbred BALB C; Microcystins; Micronucleus Tests; Real-Time Polymerase Chain Reaction; RNA

Fish suffer from anemia and hypovolemic hypotensive shock after in vivo exposure with microcystins.However, except for in vivo causes for anemia and hypotension, an in vitro study of fish erythrocytes exposed to MC is necessary. For a better understanding of hematology toxicity of MC, the main aim of the present study was to investigate the toxic effects of microcystin on fish erythrocytes in vitro. Crucian carp erythrocytes were incubated in vitro with microcystin-LR (MC-LR) at doses of 0, 1, 10, 100 and 1,000 nM.The level of lipid peroxidate significantly increased in MC-LR treatment groups. Glutathione decreased after exposure to MC-LR. The activities of antioxidative enzymes, including superoxide dismutase, catalase,glutathione peroxidase and glutathione-S-transferase,were significantly increased after exposure with MC-LR.The hemolysis was significantly increased, while the activities of acetylcholinesterase, Na?–K?-ATPase and Ca2?–Mg2?-ATPase were significantly decreased. In addition, pathological alterations in agglomerated and jagged erythrocytes were observed in blood smears. The findings indicate that damages to erythrocytes should also be responsible for anemia and hypotensive shock or even death.

Topics: Anemia; Animals; Antioxidants; Catalase; Erythrocytes; Fish Diseases; Fish Proteins; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Goldfish; Hemolysis; In Vitro Techniques; Lipid Peroxidation; Marine Toxins; Microcystins; Shock