Toxicology: Feature on erythropoiesis in dietary restricted rats

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  • ASANUMA Fumiko
    Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd.
  • MIYATA Hiroto
    Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd.
  • IWAKI Yoshinobu
    Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd.
  • KIMURA Masaaki
    Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd.

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  • Feature on Erythropoiesis in Dietary Restricted Rats

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We attempted to characterize the influence of undernutrition on erythropoiesis in toxicity studies. Male rats were divided into the following 5 groups: dietary restriction groups in which feeding was restricted by 33% or 66% for 14 days (R33 and R66); phlebotomy groups in which 1% or 4% of total blood volume was removed by serial phlebotomy for 14 days (PB01 and PB04); and a nontreated group (NT). Toxicological parameters such as hematology and blood chemistry were evaluated. The body weight gains in the R33 and phlebotomy groups (PB01 and PB04) were similar and were less than that observed in the NT group. Decreases in peripheral blood reticulocytes, bone marrow erythroids and the unsaturated iron binding capacity (UIBC) were observed as changes that suppressed erythropoiesis in the R33 and R66 groups. However, increases in reticulocytes and UIBC were observed as opposite changes in the phlebotomy groups. In addition, an increase in the blood urea nitrogen level and a decrease in the serum alkaline phosphatase level were observed as changes reflecting poor nutrition in the phlebotomy groups. Decreased reticulocytes which are related to poor nutrition were not observed. However, increases in those cells as reflected by a loss of blood were observed in the phlebotomy groups. Even if undernutrition suppresses erythropoiesis, the ability of erythropoiesis to respond to a demand appears to be retained. In repeated dose toxicity studies, decreased food consumption is often observed in the drug administration groups. Our study results provide useful information for hematological evaluations in toxicity studies.<br>

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