ABSTRACT
The aim of this study was to collect data on chronological changes in clinical laboratory tests, pathological examinations, and hepatic drug-metabolizing enzymes from Wistar Hannover rats at 8, 10, 19, and 32 weeks of age. The serum triglyceride concentration and the serum LDL cholesterol level were higher in males than in females at all ages. In contrast, serum total protein and creatinine concentrations and cholinesterase activity were lower in males than in females. In addition, sex differences were confirmed in pituitary weight and hepatic CYP3A2 and CYP2C11 activities. In conclusion, the general toxicological data noted in clinical laboratory tests, pathological examinations, and hepatic drug-metabolizing enzymes relating to chronological changes and sex differences may be useful in assessing drug-related toxicity in this strain.
Subject(s)
Rats , Toxicity Tests, Subchronic , Age Factors , Animals , Blood Chemical Analysis , Female , Liver/enzymology , Male , Rats, Wistar , Reference Values , Sex Factors , UrinalysisABSTRACT
The aim of this study was to collect data on immunological parameters from Wistar Hannover rats at 8, 10, 19, and 32 weeks of age. Low leukocyte parameter cell counts, serum globulin concentration, and T, B, and NK lymphocyte counts in peripheral blood at each time point; low T, B, and NK splenocyte counts; and high, or tendencies toward high, thymocyte counts at 10 weeks of age were noted in females when compared with males. KLH-specific antibody production increased gradually with age in both sexes. The immunological data noted for leukocyte parameters, the serum globulin concentration, and immunophenotyping (peripheral blood, spleen, and thymus) relating to chronological changes and sex differences may be useful in assessing drug-related immunotoxicity in this strain.
Subject(s)
Immune System/cytology , Leukocytes/cytology , Rats, Wistar/immunology , Animals , Female , Hemocyanins/immunology , Immune System/physiology , Immunoglobulins/blood , Immunophenotyping , Leukocytes/immunology , Lymphocyte Subsets/cytology , Lymphocyte Subsets/physiology , Male , Rats , Sex Factors , Spleen/cytology , Spleen/immunology , Thymus Gland/cytology , Thymus Gland/immunology , Toxicity Tests/methodsABSTRACT
Recently, troponin T (TnT) and troponin I (TnI) have been reported as suitable biomarkers of myocardial injury for pre-clinical toxicity studies. The purpose of the present study was to investigate the characteristics of troponins as myocardial damage biomarkers in cynomolgus monkeys. Initially, tissue distribution of biomarkers was investigated in nine organs (including the heart, liver, and kidneys) collected from naive cynomolgus monkeys. The results showed that TnT and TnI were distributed specifically in the heart, and were not detected in other tissues. Secondly, changes in blood biomarker levels and histopathological changes in cardiac tissue were investigated following myocardial injury induced by concomitant administration of isoproterenol (ISO) and vasopressin (VASO). Compared with pre-dosing, TnT and TnI were markedly increased in the ISO + VASO groups, in which severe histopathological changes including necrosis and vacuolation of muscle fibers were observed. In order to investigate the relationship of biomarker levels with the severity of myocardial injury, Spearman's correlation coefficient was calculated between C(max) and AUC and necrosis and vacuolation scores in the heart. A high correlation between necrosis and vacuolation in the heart and TnT and TnI levels was noted. These results suggest that TnT and TnI possess high sensitivity and specificity for myocardial injury in cynomolgus monkeys, and are useful biomarkers for detection of drug-induced myocardial injury in cynomolgus monkeys.
