The suppression of hematopoiesis function in Balb/c mice induced by prolonged exposure of microcystin-LR

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 mu/kg body weight (bw) every 48 h for 30d. 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 mu g/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 mu g/kg bw groups. Serum levels of some hematopoietic growth factors significantly changed in 8 mu g/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 mu g/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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.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 mu/kg body weight (bw) every 48 h for 30d. 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 mu g/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 mu g/kg bw groups. Serum levels of some hematopoietic growth factors significantly changed in 8 mu g/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 mu g/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. (C) 2013 Elsevier Ireland Ltd. All rights reserved

Global effects of subchronic treatment of microcystin-LR on rat splenetic protein levels

Microcystin-LR (MCLR), released by toxic cyanobacterial blooms, has received worldwide concerns in the past decades for its hepatotoxicity. Recent studies show that microcystins (MCs) can be accumulated in immune organs and exert notable immunotoxicity. In order to better understand cellular responses in immune tissues disrupted by MCLR treatment, this work mainly focuses on the spleen impairments of rats. After a subchronic 50 d exposure (1 or 10 mu g/kg body weight per day), spleen index, MCLR accumulation, histological change and plasma lysozyme activity were detected in MCLR-treated rat. Results indicated that prolonged exposure of MCLR led to toxin accumulation and caused severe damage in spleen of rats, and eventually impaired the immune functions. To further our understanding of the toxic effects of MCLR on the spleen and the mechanisms behind it, a proteomic analysis was performed to determine the global effects of MCLR on splenetic protein levels. In total, 48 proteins were identified and showed a significant increase or decrease in abundance compared to the control after MCLR exposure. These proteins are mainly involved in immune response, oxidative stress, energetic metabolism and the cytoskeleton assembly, indicating that MCLR exerts complex toxic effects in rat spleen and jointly results in immunotoxicity. (C) 2012 Elsevier B.V. All rights reserved.Microcystin-LR (MCLR), released by toxic cyanobacterial blooms, has received worldwide concerns in the past decades for its hepatotoxicity. Recent studies show that microcystins (MCs) can be accumulated in immune organs and exert notable immunotoxicity. In order to better understand cellular responses in immune tissues disrupted by MCLR treatment, this work mainly focuses on the spleen impairments of rats. After a subchronic 50 d exposure (1 or 10 mu g/kg body weight per day), spleen index, MCLR accumulation, histological change and plasma lysozyme activity were detected in MCLR-treated rat. Results indicated that prolonged exposure of MCLR led to toxin accumulation and caused severe damage in spleen of rats, and eventually impaired the immune functions. To further our understanding of the toxic effects of MCLR on the spleen and the mechanisms behind it, a proteomic analysis was performed to determine the global effects of MCLR on splenetic protein levels. In total, 48 proteins were identified and showed a significant increase or decrease in abundance compared to the control after MCLR exposure. These proteins are mainly involved in immune response, oxidative stress, energetic metabolism and the cytoskeleton assembly, indicating that MCLR exerts complex toxic effects in rat spleen and jointly results in immunotoxicity. (C) 2012 Elsevier B.V. All rights reserved