Effect of blood collection imitating toxicokinetic study on rat hematological parameters.

Kurata, Masahiro; Misawa, Kaoru; Noguchi, Noriko; Kasuga, Yoshitomo; Matsumoto, Kiyoshi

doi:10.2131/jts.22.3_231

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…The reduction in body weight gain observed in the phlebotomy groups in this study was in agreement with the results reported by other investigators [18,25]. Since the body weight gains in the R33 group and phlebotomy groups (PB01 and PB04) were similar, the comparative results of both were mainly described as follows.…”

Section: Discussionsupporting

confidence: 92%

“…For the removed blood volumes, 1% and 4% serial phlebotomies were selected as corresponding to slight and moderate anemic changes accompanied by slight and moderate body weight changes based on the results of previous reports [18,20,25].…”

Section: Animals and Housing Conditionsmentioning

confidence: 99%

“…Moreover, phlebotomy groups in which 1% or 4% of the total blood volume was removed by serial phlebotomy for 14 days were used as a comparative control. Phlebotomy is known to increase erythropoiesis (i.e., reticulocytosis) [6,10,18]. On the other hand, reductions in body weight have also been reported in rats that have undergone excessive blood collection [18,25].…”

mentioning

confidence: 99%

“…Phlebotomy is known to increase erythropoiesis (i.e., reticulocytosis) [6,10,18]. On the other hand, reductions in body weight have also been reported in rats that have undergone excessive blood collection [18,25]. Few reports have examined the relation between erythropoietic activity and decreased body weight gains (or undernutrition) associated with phlebotomy, to our knowledge.…”

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confidence: 99%

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Feature on Erythropoiesis in Dietary Restricted Rats

Asanuma

Miyata

Iwaki

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. 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.

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Section: Discussionsupporting

confidence: 92%

Section: Animals and Housing Conditionsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Feature on Erythropoiesis in Dietary Restricted Rats

Asanuma

Miyata

Iwaki

et al. 2011

The Journal of Veterinary Medical Science

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“…Regarding the effects of blood sampling, we considered that blood sampling had a very small influence on the phototoxicity assessment as we demonstrated in the previous study (Yonezawa et al, 2017). Additionally, sampling of less than 0.9 mL of blood per day is known as the maximum volume that can be drawn from rats without causing changes in hematological parameters (Kurata et al, 1997). In this study, the total volume of blood sampled was 0.72-0.84 mL, which is less than the 0.9 mL volume cited above.…”

Section: Discussionmentioning

confidence: 99%

Multi-site study of an <i>in vivo</i> phototoxicity evaluation in Sprague-Dawley (SD) rats aimed at incorporating the phototoxicity assessments: effects of repeated administration and toxicokinetic blood collection on drug-induced phototoxicity

Yonezawa

Katou

Kuga

2019

Fundam. Toxicol. Sci.

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The Sprague-Dawley (SD) rat has been widely used for general toxicity and toxicokinetic (TK) studies, and is also useful for phototoxicity assessments. We previously showed that phototoxicity assessments could be incorporated into general toxicity study. However, this research was performed at only one facility. Thus, the effects of repeated administration and TK blood collection were investigated in three facilities to explore the possibility of incorporating phototoxicity assessments into general toxicity study. Lomefloxacin and pirfenidone were tested as the phototoxic compounds. Six-week-old male and female SD rats were allocated to two groups for each compound: single-dose and repeated-dose. The single-dose group was irradiated after a single administration of the drug without blood collection for TK. The repeated-dose group was irradiated after 8 days of repeated administration of the drug with TK blood collection (total 0.72-0.84 mL) after the 1st and 7th administration. Phototoxic reactions on the ventral skin, dorsal skin, and auricle skin were observed macroscopically at 2, 24, 48, and 72 hr after irradiation, and skin reaction scores were evaluated. The phototoxic compounds produced skin reactions in rats at all facilities regardless of the presence or absence of repeated administration and TK blood collection. However, there were differences in the degree of skin reaction between the two groups and among the facilities. Although further studies are needed to standardize this new evaluation system, we expect that the incorporation of phototoxicity assessments will contribute to shortening the research and development period and support the 3R principle for animal experiments.

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