Time-course changes of hematology and clinical chemistry values in pregnant rats

Honda, Tatsuya; Honda, Katsuya; Kokubun, Chisato; Nishimura, Toshiaki; Hasegawa, Mina; Nishida, Atsuyuki; Inui, Toshiya; Kitamura, Kazuyuki

doi:10.2131/jts.33.375

Cited by 24 publications

(16 citation statements)

References 18 publications

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“…CHr measurement is a direct assessment of the incorporation of Fe into erythrocyte haemoglobin, and it is free from the biological variability that affects Fe, transferrin measurements, and transferrin saturation (Goodnough et al, 2000;Thomas and Thomas, 2002;Ullrich et al, 2005). Our data suggests that CHCM and CHr are critical parameters for characterizing anaemia, and this is supported by our previous study (Kojima et al, 2009) and other study (Honda et al, 2008). Classically, MTX efficacy depends on its inhibition of DHFR, resulting in depletion of intracellular reduced folates that are crucial for biosynthesis of purines and thymidilic acid, the precursors of DNA (Jolivet et al, 1983;Schornagel and McVie, 1983;Blakley, 1995).…”

Section: Discussionsupporting

confidence: 83%

Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats

et al. 2012

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-Anaemia is a significant prognostic factor in cancer patients receiving anticancer drugs such as methotrexate (MTX). This study focuses on the effects of toxicological changes on the hematopoietic systems in male and female Wistar Hannover rats when MTX is orally administered at a dose of 0, 0.05, 0.15, or 0.45 mg/(kg·day) for a period of 28 days. Both male and female rats receiving 0.45 mg/kg MTX showed a decrease in the haemoglobin concentration (Hb), haematocrit, and erythrocyte count. Female rats showed a decrease in mean corpuscular volume (MCV) and an increase in cell mean Hb (CHCM) in total erythrocytes, including the mature erythrocytes. These results indicate that MTX causes the production of small, mature erythrocytes that contain a high concentration of Hb. MTX reduced the number of peripheral reticulocytes but produced the cells with a large size and a high concentration of Hb, as demonstrated by the reticulocyte MCV and CHCM as well as the content of haemoglobin per reticulocyte (CHr). Consistent with these findings, bone marrow haematopoiesis was impaired by MTX, as there was a reduction in erythroid count in rats of both sexes. The number of cells of the myeloid lineage reduced in female rats, followed by a reduction in the total leukocyte and neutrophil counts in peripheral blood. Thrombocytopenia was detected in a small population of rats. These results indicate that MTX induces hyperchromic microcytic anaemia and pancytopenia, and the use of MCV and CHCM in mature erythrocytes and reticulocytes, along with the CHr, gives a better understanding of the development and nature of anaemia.

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Section: Discussionsupporting

confidence: 83%

Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats

et al. 2012

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“…Pregnant rats exposed to a low-sodium diet show a decrease in sodium and an increase in potassium, whereas non-pregnant rats do not (36). Honda et al reported similar results for rats fed standard fodder (37).…”

Section: Test (Y)mentioning

confidence: 88%

Laboratory reference intervals during pregnancy, delivery and the early postpartum period

Klajnbard

Szecsi²,

Colov³

et al. 2009

Clinical Chemistry and Laboratory Medicine

102

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Background: Physiological changes during pregnancy may affect laboratory parameters. Reference values based on samples from non-pregnant women are not necessarily useful for clinical decisions during pregnancy. There is a need to establish reference values during pregnancy in order to recognize pathological conditions. Methods: Eight hundred and one women with expected normal pregnancies were included in the study. Of these, 391 had no complications during pregnancy, delivery, or the early postpartum period. Blood samples were obtained at gestational weeks 13-20, 21-28, 29-34, 35-42, at labor, and 1 and 2 days postpartum. Reference intervals were calculated for 36 tests as recommended by the International Federation of Clinical Chemistry and Laboratory Medicine. Results: Many tests showed such large variations indicating that gestational age-specific reference intervals were necessary. Other tests had different but stable values when compared to non-pregnant women. A minor decrease in albumin levels was observed. This was not only due to pregnancyassociated hemodilution, since other components with the same or a larger molecular diameter did not show a similar decrease. Many tests exhibited a broad distribution around vaginal delivery and in the early postpartum period. Conclusions: Only a few parameters were unaffected during uncomplicated pregnancy, delivery, and the early postpartum period suggesting that implementation of gestational agespecific reference intervals is necessary. Clin Chem Lab Med 2010;48:237-48.

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“…However, there are almost no reports of effects of PB on blood coagulation time in pregnant or lactating dams and their pups, although they are widely used in reproduction studies. In addition, -es are observed in blood parameters in rats and rabbits as well as in women (Mizoguchi et al, 2009;Urasoko et al, 2009;Honda et al, 2008;De Rijk et al, 2002;Katoh et al, 1992;Wells et al, 1999). Therefore, this study was performed to clarify the effects of PB administration on blood coagulation-related parameters in nonpregnant or pregnant rats and in lactating rats and their pups.…”

Section: Introductionmentioning

confidence: 97%

Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups

et al. 2009

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-Effects of repeated administration of phenobarbital (PB) on blood coagulation-related parameters were examined in non-pregnant, pregnant and lactating rats, and also in pups born to PB-treated lactating dams. PB was orally administered at a dose level of 80 mg/kg/day to pregnant (from gestation day (GD) 13), postpartum (from postpartum day (PPD) 7) and non-pregnant rats (from 13 weeks of age) for 7 days. Blood was collected on GD20 or PPD14 to perform blood coagulation examination. Concurrently, the blood coagulation parameters were examined in the pups. Increases in liver weight and/or hepatic cytochrome P450 content were observed in the PB-treated non-pregnant, pregnant and lactating rats. Activated partial thromboplastin time (APTT) was prolonged and anti-thrombin III (ATIII) concentration was increased in the lactating rats, while there were no changes in prothrombin time (PT) or APTT in the non-pregnant and pregnant rats. Moreover, prolongation of PT and APTT and decreases in factors VII and IX activities were observed in their pups. Thus, prolongation of blood coagulation time was con-2 (VK 2 ) on PB-induced changes in blood coagulation-related parameters of both dams and their pups were examined by co-administration with PB and VK 2 to lactating dams. PT and APTT were comparable to the control and PB-induced prolongation of blood coagulation time was improved in the pups while APTT was prolonged in dams, suggesting that VK 2

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Time-course changes of hematology and clinical chemistry values in pregnant rats

Cited by 24 publications

References 18 publications

Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats

Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats

Laboratory reference intervals during pregnancy, delivery and the early postpartum period

Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups

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