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Effects of four-week feed restriction on toxicological parameters in beagle dogs.

Takamatsu K, Yamashita H, Satake S, Kazusa K, Tabata H, Nishikata T - Exp. Anim. (2015)

Bottom Line: Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations.The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology).In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology.

View Article: PubMed Central - PubMed

Affiliation: Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.

ABSTRACT
This study was conducted to examine any changes caused by feed restriction in dogs to contribute to safety evaluation in toxicity studies. Two male 7-month-old beagle dogs/group were fed 300 (control), 150 (50% of control), or 70 g/animal of diet daily (23% of control) for 4 weeks. Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations. The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology). In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology. These results provide important reference data for distinguishing the primary effects of test compounds from secondary effects of decreased food consumption in toxicity studies in beagle dogs.

No MeSH data available.


Related in: MedlinePlus

Histological section of the stomach at 70 g/day. Scale bars: A, 100μm; B, 50 μm. A: A regenerative mucosa can beseen in the right half area of the picture. B: Regenerative mucosa, magnified image.The cytoplasm of the epithelium shows basophilia. Mitotic figures can be seen(arrows).
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fig_008: Histological section of the stomach at 70 g/day. Scale bars: A, 100μm; B, 50 μm. A: A regenerative mucosa can beseen in the right half area of the picture. B: Regenerative mucosa, magnified image.The cytoplasm of the epithelium shows basophilia. Mitotic figures can be seen(arrows).

Mentions: Histological section of the sternal bone marrow. Scale bars: A to C, 100μm; D to F, 50 μm. A: 300 g/day. B: 150 g/day.C: 70 g/day. D: 300 g/day, magnified image. E: 150 g/day, magnified image. F: 70g/day, magnified image. Hypocellularities are observed in B and C, andhypocellularity and an increase in the mature granulocyte ratio are observed in Eand F.


Effects of four-week feed restriction on toxicological parameters in beagle dogs.

Takamatsu K, Yamashita H, Satake S, Kazusa K, Tabata H, Nishikata T - Exp. Anim. (2015)

Histological section of the stomach at 70 g/day. Scale bars: A, 100μm; B, 50 μm. A: A regenerative mucosa can beseen in the right half area of the picture. B: Regenerative mucosa, magnified image.The cytoplasm of the epithelium shows basophilia. Mitotic figures can be seen(arrows).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548000&req=5

fig_008: Histological section of the stomach at 70 g/day. Scale bars: A, 100μm; B, 50 μm. A: A regenerative mucosa can beseen in the right half area of the picture. B: Regenerative mucosa, magnified image.The cytoplasm of the epithelium shows basophilia. Mitotic figures can be seen(arrows).
Mentions: Histological section of the sternal bone marrow. Scale bars: A to C, 100μm; D to F, 50 μm. A: 300 g/day. B: 150 g/day.C: 70 g/day. D: 300 g/day, magnified image. E: 150 g/day, magnified image. F: 70g/day, magnified image. Hypocellularities are observed in B and C, andhypocellularity and an increase in the mature granulocyte ratio are observed in Eand F.

Bottom Line: Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations.The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology).In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology.

View Article: PubMed Central - PubMed

Affiliation: Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.

ABSTRACT
This study was conducted to examine any changes caused by feed restriction in dogs to contribute to safety evaluation in toxicity studies. Two male 7-month-old beagle dogs/group were fed 300 (control), 150 (50% of control), or 70 g/animal of diet daily (23% of control) for 4 weeks. Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations. The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology). In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology. These results provide important reference data for distinguishing the primary effects of test compounds from secondary effects of decreased food consumption in toxicity studies in beagle dogs.

No MeSH data available.


Related in: MedlinePlus