Age-related Susceptibility to Induction of Osteochondral and Vascular Lesions by Semicarbazide Hydrochloride in Rats

Abstract

To compare the susceptibility to toxicity of semicarbazide hydrochloride (SEM-HCl) between young and adult rats, 3- and 20-week-old female SD rats were given a diet containing SEM-HCl at 0, 500, or 1,000 ppm and 0 or 1,000 ppm, respectively, for 4 weeks. Half of the animals were then maintained on basal diet for a further 2 weeks as recovery groups. Only in young rats was deformation of the knee joints as well as thorax and tail observed at 500 and 1,000 ppm. Histopathologically, severe osteochondral lesions, such as disarrangement and thickening of the epiphyseal cartilage and deformation of articular cartilage, were observed, but the severity of these lesions became reduced during the recovery period. In adult rats, osteochondral lesions were relatively mild. Fissures in the cartilage matrix of the tibia were characteristic of adult rats, and in these, reduction of severity was not obvious in the recovery group. In the thoracic aorta, the appearance of elastic laminae was altered only in young rats in both the 4-week treatment and recovery groups. These results suggest that growing animals are more susceptible to toxicity of SEM-HCl than adults are. Effects and the induced lesions link to the developing stage of the target organs.