As part of a collaborative work, male rats were administered 1,3-dinitrobenzene (1,3-DNB) daily at 0, 25 and 50 mg/kg/day from the age of 6 weeks for 4 weeks (4-week exp.), or at 25, 50 and 75 mg/kg/day from the age of 8 weeks for 2 weeks (2-week exp.). After the end of each administration period, all survivors were sacrificed, and their testes and epididymides were removed, weighed and examined histopathologically. The following results were obtained. In the 4-week exp.: At 50 mg/kg/day, the weights of testes and epididymides showed decrease with macroscopic atrophy. The testicular spermatogenic epithelium showed decrease in the number of sperm-spermatocytes, degeneration/necrosis, giant cell formation and vacuolation, reduction in sperm counts also being evident in the ducts of the epididymides. In the 2-week exp.: At 50 and 75 mg/kg/day, the weights of testes and/or epididymides showed decrease with macroscopic atrophy. Several histopathological changes in the testes and epididymides were essentially the same changes as in the group given 50 mg/kg/day in the 4-week exp., with a clear relation. These results indicate that a 2-week administration period is sufficient to detect testicular and epididymal histopathological changes induced by 1,3-dinitrobenzene in male rats.
In this study, a new simple method to measure erythrocyte fragility with stirring of diluted blood (stirring method) was introduced and evaluated with anemic rats given beta-acetylphenylhydrazine (APHZ) or clofibrate. APHZ at a dose of 40 mg/kg caused significant decreases in hemoglobin and hematocrit 24 hr after administration. However, the marked elevation of erythrocyte fragility was already detectable after 6 hr by our stirring method. At a dose of 10 mg/kg APHZ, although no significant changes in the erythrocytic parameters were observed throughout the experimental period (72 hr), the blood stirring method revealed a marked elevation of erythrocyte fragility 6 hr after administration. Similarly with clofibrate, no changes in erythrocytic parameters were noted following 100 mg/kg or 300 mg/kg administration, but the enhanced fragility was evident with the stirring method. Thus, using our approach, the erythrocyte fragility could be detected at an earlier stage and with greater sensitivity than by decreases in erythrocytic parameters. The results suggest that the stirring method will prove to be useful for detecting erythrocyte fragility in safety studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.