Effect of Feed Restriction on Peripheral Blood and Bone Marrow Cell Counts of Wistar Rats

Ogawa, Yukio; Matsumoto, Kiyoshi; Kamata, Eiichi; Ikeda, Yasukazu; Kaneko, Toyozo

doi:10.1538/expanim1978.34.4_407

Cited by 24 publications

(21 citation statements)

References 16 publications

(5 reference statements)

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“…Ogawa et al . reported that dietary restriction strongly influences the reticulocytes in peripheral blood 5 . We previously reported that the influence of undernutrition on erythroblastic changes cannot be disregarded in 14-day toxicity studies 10 , 11 .…”

Section: Discussionmentioning

confidence: 98%

Evaluation of Short-term Myelotoxicity Study in Dietary Reduced Rats

et al. 2010

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This study attempted to prove our hypothesis that a short-term toxicity study, using a 4-day dosing regimen as an example, is suitable for evaluating myelotoxicity in rats. We compared the hematological, bone marrow cytological and histopathological results of 5-fluorouracil (5-FU) treated and pair-feeding groups after a 4-day administration period. Several experimental groups were defined for this 4-day study as well as for our previously reported 14-day study (Miyata et al., 2009); these included 5-FU treated groups receiving 12, 15 and 18 mg/kg/day (FU12, FU15 and FU18), pair-feeding groups (R12, R15 and R18 receiving the same amount of food as the FU12, FU15 and FU18 groups, respectively) and a nontreated control group. Although severe reductions in body weight gain and food consumption were reported in the 14-day study, only slight reductions were observed in the 4-day study. In the 4-day study, a decrease in blood reticulocytes and a decreasing trend of marrow erythroid cells were only observed in the FU18 group, and no effects were observed in the pair-feeding groups. The erythroblastic changes observed in this 4-day study were thought to reflect the direct influence of 5-FU administration. Since concerns regarding the influence of secondary changes related to undernutrition were minimized in the 4-day study, it was thought to clarify the direct influence of 5-FU administration on erythroblastic cells. Thus, a 4-day study protocol might be helpful for distinguishing secondary changes related to undernutrition.

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Section: Discussionmentioning

confidence: 98%

Evaluation of Short-term Myelotoxicity Study in Dietary Reduced Rats

et al. 2010

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“…Indeed, our studies have demonstrated that dietary exposure of mice to 0.02% (w/w) PFOS or PFOA reduces their food intake to approximately 65% and 75%, respectively, of the amount consumed by untreated animals (Qazi et al, 2009;and present study). Severe caloric restriction is known to substantially reduce the numbers, chemotaxis and phagocytic activity of neutrophils in the bone marrow pool, as well as in the peripheral blood of rats (Suda et al, 1976;Ogawa et al, 1985;Garcia and Barbieri, 1986;Levin et al, 1993;Slapnickova and Berger, 2002). In addition, moderate caloric restriction is known to reduce thymic and splenic weight and cellularity, as well as the numbers of CD4 + CD8 + thymocytes and splenic B-lymphocytes (Hishinuma et al, 1990;Poetschke et al, 2000;Savino, 2002;Martin et al, 2008) and to alter the nucleolar structure and function in lymphocytes (Berger et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

High-dose, short-term exposure of mice to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) affects the number of circulating neutrophils differently, but enhances the inflammatory responses of macrophages to lipopolysaccharide (LPS) in a similar fashion

et al. 2009

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“…Drug-induced myelotoxicity has been shown in short-term studies 24,25 . Ogawa et al 26 and Levin et al 5 reported decreases in white blood cell, reticulocyte, and nucleated cells or other blood cells in marrow counts following dietary restriction in the rat. Matsumoto 24 reported a reduction in the bone marrow cell count with an elevation of the G/E ratio in food-restricted rats.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Myelotoxicity in Dietary Restricted Rats

et al. 2009

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The purpose of this study was to clarify the effect of decreased food consumption on evaluation of myelotoxicity in routine general toxicity studies. Male rats were divided into the following 7 groups: 12, 15, and 18 mg/kg 5-fluorouracil (5-FU) treatment groups (FU12, FU15 and FU18); dietary restriction groups (R12, R15 and R18 receiving the same amount of food as the rats in the FU12, FU15 and FU18 groups, respectively); and a nontreated control group (NT). We compared the changes in body weight, hematology and the results of cytological analyses of bone marrow and histopathology among the groups after administration and recovery periods of 14 and 7 days, respectively. At the end of the administration period, the FU15 and FU18 groups showed decreases in many hematologic and bone marrow parameters that were all similar to those in the corresponding dietary restriction groups (R15 and R18). A granulocyte abnormality (polyploidy: frequency of 1% or less) was also observed in all 5-FU treated groups. At the end of the recovery period, increases in the reticulocyte and platelet counts and extramedullary hematopoiesis of the spleen were observed in the 5-FU treated groups. These results indicate that the results of general toxicity studies in rats should be evaluated in consideration of dietary restriction effects when food consumption is decreased at about 30-40% or more. Careful morphological observation of hemocytes would be helpful in distinguishing the effect of a drug from that of dietary restriction in relation to hematological and bone marrow parameters. Performance of a recovery test to determine the reactive response of hematopoiesis is also recommended.

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Effect of Feed Restriction on Peripheral Blood and Bone Marrow Cell Counts of Wistar Rats

Cited by 24 publications

References 16 publications

Evaluation of Short-term Myelotoxicity Study in Dietary Reduced Rats

Evaluation of Short-term Myelotoxicity Study in Dietary Reduced Rats

High-dose, short-term exposure of mice to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) affects the number of circulating neutrophils differently, but enhances the inflammatory responses of macrophages to lipopolysaccharide (LPS) in a similar fashion

Evaluation of Myelotoxicity in Dietary Restricted Rats

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