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

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.

Effects of reduced food intake for 4 weeks on physiological parameters in toxicity studies in dogs

“…Other significant findings observed in this study were similar to those reported previously (Morita et al, 2015;Takamatsu et al, 2015). The following results have thus been reproducibly observed in reduced food intake studies: a decrease in body weight; a decrease in the WBC count (especially the Neut count); decreases in the AST, LDH, and Ca levels; an increase in the CRE level; a decrease in the thymus weight; and mild atrophy in the thymus.…”

“…The blood chemistry results showed a decrease in the ALP level, similar to previously reported findings (Morita et al, 2015;Takamatsu et al, 2015). In the present study, ALP isozymes were assayed to confirm which organs were affected by the reduced food intake.…”

“…In the electrocardiography studies, a decrease in the HR with a subsequent prolongation of the QRS duration and a tendency toward a prolonged PR interval were observed in this study, and similar changes have been previously reported to be associated with a reduced food intake (Morita et al, 2015;Takamatsu et al, 2015) or malnutrition (Alden et al, 1987). Body weight loss associated with changes in diet reportedly affects autonomic nervous activity in dogs (Rocchini et al, 1989;Hall et al, 1993;Truett et al, 1996).…”

“…In addition, a decrease in the weight of the liver was observed in the LF group. A reduced food intake is known to affect the weight of the liver in dogs (Takamatsu et al, 2015) and rats (Schwartz et al, 1973;Oishi et al, 1979;Pickering and Pickering, 1984;Levin et al, 1993;Seki et al, 1997;Yoshii et al, 2003;Moriyama et al, 2008), and the liver weight is reportedly associated with variations in the water and glycogen contents arising from feeding in rats (Leveille and Chakrabarty, 1967;Rothacker et al, 1988). Thus, the decrease in the weight of the liver observed in the LF group in the present study was considered to be mainly related to a decrease in glycogen.…”

“…A tendency toward a decreased circulating plasma volume was also observed in the LF group. Water intake is reportedly correlated with eating in experimental animals (Kraly, 1984), and a decrease in water consumption has been reported in dogs subjected to a reduced food intake (Takamatsu et al, 2015). The change in the circulating plasma volume was considered to have been caused by a decrease in water consumption.…”