Abstract:The modifying effects of liver injury on male reproductive organ toxicity of di-n-butyl phthalate (DBP) were studied using male F344 rats. Seventy-two male animals, aged 10 weeks at the commencement, were divided into 8 groups of 9 rats each. Groups 1 to 4 were given 200 mg/kg bw of thioacetamide (TAA) intraperitoneally 3 times / week, while Groups 5 to 8 were injected with the PBS vehicle only. From 1 week after the start, groups 1 and 5, 2 and 6, and 3 and 7 were given daily 500, 125, 31.25 mg/kg bw of DBP, respectively (23 times) for 4 weeks, while groups 4 and 8 served as vehicle controls. As the result of our treatment, liver injury was induced in the animals, and the liver injury was confirmed by histopathological findings and serum transaminase levels at sacrifice. Enhancement of rat male reproductive organ toxicity of DBP under liver injury status was also seen. The relative organ weights of prostate, bilateral seminal vesicles, bilateral epididymides and bilateral testes, and the sperm number and motility rate were decreased. Also the sperm abnormality rate was increased under liver injury. Furthermore histopathological abnormality of the testis, such as absence of germ cells and the presence of Sertoli cells only was seen in the rats treated with TAA and high dose of DBP, however neither the serum nor testicular testosterone levels varied in the present study. The sperm number and relative weight of bilateral epididymides were decreased by TAA treatment only, unrelated to DBP treatment. These facts suggest that liver injury can not only enhance the rat male reproductive organ toxicity of DBP, but also induce such toxicity by itself. (J Toxicol Pathol 2004; 17: 177-185)
Abstract:In the present study, a suitable rat model for testing the modifying effect of liver injury on the rat male organ toxicity of endocrine disrupters was researched using thioacetamide (TAA) and carbon tetrachloride (CCl 4 ) as liver toxicants. Male 8-week-old F344 rats were divided into six groups as follows. Animals in groups 1 and 2 were given 200 and 100 mg/kg body weight of TAA with PBS by intraperitoneal injection (ip.) 3 times a week for 4 weeks, respectively. Group 3 was given PBS only. Animals in groups 4 and 5 were given 2 and 1 mg/kg body weight of CCl 4 with corn oil by subcutaneous injection (sc.) once a week, for 4 weeks, respectively. Group 6 was given corn oil only. Three rats from each group were sacrificed at week 4 and the rest of groups 1 and 4 were sacrificed after a further 4 weeks of withdrawal period. In the animals administered 200 mg/kg of TAA the findings of apparent liver damage on both histopathological and biochemistrical examinations could be seen: fibrosis, enlargement of Glisson's sheath and infiltration of inflammatory cells in the liver, and apparent elevation of serum aspartate aminotransferase and alanine aminotransferase levels. On the other hand, in the animals administered 2 mg/kg of CCl 4 only the histopathological findings of liver damages could be seen: fatty and inflammatory changes in liver. In the animals administered 100 mg/ kg of TAA or 1 mg/kg body weight of CCl 4 only the histopathological findings of slight inflammatory changes in their liver samples. However these findings of liver damage were almost completely absent after the 4-week withdrawal period. ( For many years, modern industry and agriculture have produced various environmental pollutants, and the risk of human exposure to these chemicals has increased. Recently, some of these pollutants have been paid attention as endocrine disrupters and many valuable studies about them have been performed. However, there are a number of uncertainties, and there is little information about how endocrine disrupters act on humans with various degrees of organ failure. Most chemicals are metabolized in the liver, and it is well known that the effects of some drugs are enhanced under liver dysfunction. Thus, the effect of some endocrine disrupters may also be enhanced under liver dysfunction. However, there have been no reports concerning this issue and especially, a suitable rat model for researching how liver dysfunction modifies the effect of endocrine disruptors has not been established. The present study was designed to gain information on a suitable rat liver injury model. The model must satisfy some important criteria. First, the effect of endocrine disrupters should be tested using young animals, so the period for inducing liver injury should be not long; it was designed as 4 weeks in our study. Second, the degree of liver damage should not be too severe, because liver dysfunction can show male sex organ toxicity by itself, and may mask the target effect of endocrine disrupters [1][2][3] . Third, the liver...
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