BACKGROUND: The Wistar Hannover rat has been considered as an alternative animal model to the Sprague-Dawley rat in the safety evaluation of candidate pharmaceuticals for potential reproductive and developmental toxicity. Hematology and clinical chemistry results may provide useful evidence of maternal toxicity in the absence of fetal effects. OBJECTIVE: The purpose of this study was to evaluate differences in routine laboratory values between nonmated and pregnant (near-term)Wistar Hannover rats during a control developmental study. METHODS: One hundred fifty pregnant female Wistar Hannover rats (Tac:Glx:WlfBR) were dosed orally once per day with distilled water from gestation days (GDs) 6 through 17. An additional 150 nonmated (nonpregnant) females used as age-matched controls were dosed from study days (SDs) 7 through 18. Blood samples were collected on GD 18 or 19 (SD 19 or 20) for routine hematology and plasma clinical chemistry tests. Reference intervals were established for pregnant and nonmated animals. RESULTS: On GD 18/19, pregnant rats had a lower RBC count, hemoglobin concentration, and HCT, and higher MCH, MCHC, reticulocyte percentage, and platelet, WBC, absolute reticulocyte, segmented neutrophil, lymphocyte, and monocyte counts compared with nonmated rats. Pregnant rats had lower albumin, glucose, urea, and chloride concentrations, lower creatine kinase and alkaline phosphatase activities, higher total bilirubin, cholesterol, triglyceride, calcium, phosphorus, and globulin concentrations, and higher ALT activity than nonmated rats. Serum triglyceride concentration was approximately fourfold higher in pregnant rats compared with nonmated controls. CONCLUSION: Differences in hematology and chemistry values in pregnant Wistar Hannover rats are similar to those in Sprague-Dawley rats and support use of the Wistar Hannover rat as an animal model in the assessment of maternal toxicity. Differences in laboratory values of pregnant rats should be considered when interpreting data following exposure to candidate pharmaceuticals.
BACKGROUND: The Wistar Hannover rat has been considered as an alternative animal model to the Sprague-Dawley rat in the safety evaluation of candidate pharmaceuticals for potential reproductive and developmental toxicity. Hematology and clinical chemistry results may provide useful evidence of maternal toxicity in the absence of fetal effects. OBJECTIVE: The purpose of this study was to evaluate differences in routine laboratory values between nonmated and pregnant (near-term)Wistar Hannover rats during a control developmental study. METHODS: One hundred fifty pregnant female Wistar Hannover rats (Tac:Glx:WlfBR) were dosed orally once per day with distilled water from gestation days (GDs) 6 through 17. An additional 150 nonmated (nonpregnant) females used as age-matched controls were dosed from study days (SDs) 7 through 18. Blood samples were collected on GD 18 or 19 (SD 19 or 20) for routine hematology and plasma clinical chemistry tests. Reference intervals were established for pregnant and nonmated animals. RESULTS: On GD 18/19, pregnant rats had a lower RBC count, hemoglobin concentration, and HCT, and higher MCH, MCHC, reticulocyte percentage, and platelet, WBC, absolute reticulocyte, segmented neutrophil, lymphocyte, and monocyte counts compared with nonmated rats. Pregnant rats had lower albumin, glucose, urea, and chloride concentrations, lower creatine kinase and alkaline phosphatase activities, higher total bilirubin, cholesterol, triglyceride, calcium, phosphorus, and globulin concentrations, and higher ALT activity than nonmated rats. Serum triglyceride concentration was approximately fourfold higher in pregnant rats compared with nonmated controls. CONCLUSION: Differences in hematology and chemistry values in pregnant Wistar Hannover rats are similar to those in Sprague-Dawley rats and support use of the Wistar Hannover rat as an animal model in the assessment of maternal toxicity. Differences in laboratory values of pregnant rats should be considered when interpreting data following exposure to candidate pharmaceuticals.
Authors: N Bezdieniezhnykh; A Lykhova; T Kozak; T Zadvornyi; T Borikun; O Voronina; N Lukianova Journal: BMC Pharmacol Toxicol Date: 2022-06-08 Impact factor: 2.605