图象采集系统在大鼠睾丸毒性病理诊断中的应用探讨

目的：利用图象采集系统对二乙氧基乙醇引发的睾丸毒性进行病理定量分析,使组织形态变化结果的表达更加量化.方法：以400、800、1200、1600 mg/kgBW二乙氧基乙醇经口给予大鼠,连续染毒7 d,对睾丸进行光镜病理组织学检查并利用图象采集系统对睾丸曲细精管直径进行测量.结果：染毒7 d大鼠各组生精过程受到不同程度抑制,睾丸重量明显减轻（P＜0.01）,镜下观察睾丸各级生精细胞,精子发生退行性改变,曲细精管直径测量各染毒组比对照组明显变小（P＜0.01）.结论：利用图象采集系统对大鼠睾丸曲细精管直径测量,与睾/体比、细胞形态观察结果较为一致,对睾丸生殖毒性组织损伤的量化起到一定的作用,可以作为评价睾丸生殖毒性的指标之一.     

Developmental toxicity potential of paclobutrazol in the rat

Paclobutrazol is used as a fungicide and as a plant growth regulator, but there are few studies about its potential toxic effects. Experiments were conducted to determine whether this compound has adverse effects on the reproduction and development of offspring. The influence of 1.0 mg/kg paclobutrazol (10 x the acceptable daily intake-ADI), by oral exposure during gestational organogenesis of rats, was evaluated on maturational and behavioural aspects of offspring development. This dose did not promote evidence of maternal toxicity and the weight of gravid uterus, fetus, and ovary on days 16 and 20 of pregnancy were not affected. Also, the pesticide did not affect body weight gain of the dams and offspring. However, the pups' survival at weaning was impaired by paclobutrazol. Beyond that, study of the functional state of rat pups' nervous system at different stages of postnatal development revealed some differences in treated ones. Damage was observed in the expression of acoustic startle reflex and altered locomotion and/or rearing in an open-field apparatus in treated pups depending on their age. There were no observed alterations in swimming behaviour. The data support further studies of the potentially toxic effects that exposing mothers to this pesticide may have on their litters.     

硫酸镍对大鼠睾丸细胞损伤作用

目的 探讨硫酸镍( NiSO4)对雄性大鼠生殖系统损伤的可能机制.方法 选择雄性大鼠32只,随机分为4组,对照组,NiSO41.25、2.50、5.00 mg/kg组;采集附睾和睾丸样本,分别检测精子活率和密度,睾丸细胞活性氧自由基(ROS)荧光强度及其Bax、caspase -3蛋白表达水平.结果 NiSO4 2.50和5.00 mg/kg组大鼠精子活率(分别为68.29％ 、65.29％)和密度(分别为3.03、2.85×106/mL)均明显低于对照组(82.34％和4.80×106/mL)(P＜0.05);睾丸细胞ROS荧光强度(98.59和96.43)则明显高于对照组(62.54)(P＜0.01).与对照组比较,NiSO4 2.50和5.00 mg/kg组Bax蛋白表达量明显升高(P＜0.01),各NiSO4组大鼠睾丸细胞caspase -3前体蛋白表达量明显升高(P＜0.05),且均出现caspase -3切割片段,后者呈剂量效应关系.结论 过量NiSO4暴露可诱导睾丸细胞内大量生成ROS,进而上调Bax蛋白表达并激活caspase -3蛋白,终致生殖损伤发生.     

Testicular histopathology in juvenile rat toxicity studies

Histopathologic interpretation of juvenile toxicity studies is necessarily complicated by the dynamic developmental processes underway within the test subjects. In addition to potentially marked differences in compound metabolism, juvenile animals have vulnerable temporally defined proliferating cell populations compared to their adult counterparts. Pathologists require an understanding of developmental processes and conditions underway during exposure to the compound(s) in a juvenile toxicity study in order to interpret the terminal histopathology accurately. Postnatal testicular development in rats affords an example of how developmental considerations are essential to understanding toxic effects. This review provides an overview of testicular histology and pre- and postnatal testicular development, examples of juvenile rat testicular toxicity from the literature, and considerations for designing juvenile studies for safety assessment of pharmaceutical compounds.     

Inhibition of testicular steroidogenesis in the neonatal rat following acute ethanol exposure

We have previously reported detrimental effects of in utero ethanol exposure on testicular steroidogenic enzyme activity in newborn rats. It is now reported that in utero ethanol exposure during Day 12 of gestation through birth has no apparent morphological effect on the testes of Day 1 neonatal rats. It appears that the detrimental effects of ethanol on testicular steroidogenesis can be manifested at the biochemical level in the absence of morphological effects. However, it remained unknown as to whether acute exposure to ethanol would elicit similar biochemical effects as chronic ethanol exposure on testicular steroidogenesis. To test this possibility ethanol was injected at 0, 1, or 2 g/kg intraperitoneally (IP) into rats of various postnatal ages. Plasma ethanol and testosterone levels as well as testicular 17 alpha-hydroxylase and C17,20-lyase activities were measured. The results indicate that acute exposure to ethanol significantly (p less than 0.05) inhibits the catalytic activity of testicular 17 alpha-hydroxylase in the newborn rat testis. This inhibition was specific since the activity of testicular C17,20-lyase was not affected. In conjunction with the reduction in testicular enzyme activity, plasma testosterone levels were reduced to 30% of the control levels in newborn animals receiving ethanol. In older animals, i.e., postnatal Day 20 and 40 rats, plasma testosterone levels were reduced, but not significantly, following ethanol treatment. Furthermore, testicular enzyme activity was not significantly reduced following ethanol treatment in these same older animals. These results suggest that the newborn rat testis is especially sensitive to the effects of ethanol.     

Subchronic oral toxicity of tributoxyethyl phosphate in the Sprague-Dawley rat

The effects of the widely used alkyl phosphate, tributoxyethyl phosphate (TBOP), were investigated in male and female Sprague-Dawley rats. This chemical was administered (low dose: 0.25 ml/kg X day; high dose: 0.50 ml/kg X day) by gavage once a day for 5 days/wk, over a period of 18 wk. Histopathological examination of tissues in treated male rats showed the presence of cardiac lesions, including myocardial necrosis with inflammatory cell infiltration. This study indicated that oral administration of TBOP may have caused or contributed to the early onset of a common background finding in this rat strain.     

Subacute inhalation toxicity of benzaldehyde in the Sprague-Dawley rat.

Benzaldehyde was administered by inhalation to female and male Sprague-Dawley rats for 14 consecutive days (low level: 500 ppm; medium level: 750 ppm; high level: 1000 ppm). Effects of this chemical were investigated during and at the end of the exposure period. Throughout the experiment, significant hypothermia and a reduction of motor activity were observed in all rats exposed to benzaldehyde and were accompanied in high-level rats by a severe impairment of the central nervous system, as evidenced by abnormal gait, tremors, and a positive Straub sign. Histopathologic examination of tissues from exposed rats showed a goblet cell metaplasia that was largely confined to the respiratory epithelium lining the nasal septum in male rats. No other abnormal microscopic changes were observed. A no effect level was not observed in these studies.     

Nutritional availability and chronic toxicity of selenocyanate in the rat

To evaluate nutritional availability and chronic toxicity of KSeCN, female postweanling rats were fed casein-based diets plus 0.1, 0.5, 2.5, 5 and 10 mg Se/kg as KSeCN for 6 wk, or 0.1, 0.5 and 10 mg Se/kg as Na2SeO3. A control group was fed the basal diet (Se = 0.04 mg/kg) and one group was fed the basal diet plus 5 mg Se/L as KSeCN in the drinking water. There were no differences in weight gain and diet consumption among groups fed 2.5 mg Se/kg or less. At 5 and 10 mg Se/kg, rats showed depression in weight gain and diet consumption. After wk 6 there were no abnormalities of the major organs of rats fed 2.5 mg Se/kg or less. Spleen enlargement was observed at 5 and 10 mg Se/kg, and liver damage and kidney enlargement at 10 mg Se/kg. Se content in the blood, liver and kidney of rats fed KSeCN was generally somewhat lower than for those fed Na2SeO3 at the same levels. The availability of Se from KSeCN for glutathione peroxidase formation in blood, liver and kidney was comparable to that of Na2SeO3. Plasma thyroxine in groups fed 10 mg Se/kg was 40% of that in the control group, but was not altered at lower Se levels.     

Cocaethylene toxicity in rat primary myocardial cell cultures

Cocaethylene is a unique cocaine metabolite formed in the presence of ethanol by the liver. Neither acute nor chronic cardiotoxic effects of this metabolite have been investigated. The purpose of this study was to establish a time- and dose-dependent toxicity profile for cocaethylene in primary myocardial cell cultures established from 3–5-day-old Sprague-Dawley rats. Alterations in lactate dehydrogenase (LDH) release, lysosomal neutral red (NR) retention, thiobarbituric acid-reactive substances (TBARS), morphology, and beating activity were evaluated after treatment of cultures with cocaethylene doses ranging from 1.0 × 10⁻³ to 1.0 × 10⁻⁹ M from 1 to 24 h. LDH release was significantly elevated after 24 h only with those cultures exposed to the highest dose of cocaethylene (1.0 × 10⁻³ M). The highest dose of cocaethylene also significantly depressed NR retention. While all doses of cocaethylene depressed contractile activity and altered cellular morphology by 24 h, there were no TBARS formed up to 15 h. Thus, both low and high doses of cocaethylene are injurious to the cellular integrity and contractility of myocardial cell cultures. Future studies are warranted to determine mechanisms of cocaethylene toxicity in this in vitro model of spontaneously contracting myocardial cells.     

中生菌素可湿性粉剂的大鼠急性毒性研究

目的 研究质量分数为3%的中生菌素可湿性粉剂不同染毒途径染毒的大鼠急性毒性。方法 每组10只大鼠(雌雄各半),经口、经皮均采用一次性大剂量染毒方式,剂量分别为5 000 mg/kg和2 000 mg/kg。呼吸道以悬浮液经气溶胶发生装置雾化后染毒2 h,每组10只大鼠,剂量为1 126 mg/m³、2 031 mg/m³、2 501 mg/m³、3 539 mg/m³、4 464 mg/m³。连续观察大鼠毒性症状和体征14 d,并对吸入毒性实验大鼠的肺部进行组织学检查。结果 经口、经皮染毒大鼠未见明显中毒症状;经呼吸道染毒引起呼吸系统症状为主的毒性反应,大体剖检显示肺脏充血、出血,体积增大;病理检查发现肺组织结构破坏、肺泡隔大小不一,肺泡壁增粗、断裂,肺间质大量中性粒细胞浸润及红细胞外渗,可见血管内皮细胞增生;肺组织病理半定量评分提示染毒剂量越高引起的肺损伤越明显。结论 中生菌素可湿性粉剂的悬浮液经呼吸道吸入,可引起大鼠肺脏损伤。     

Influence of dietary selenium on lead toxicity in the rat.

An investigation of the influence of dietary selenium (0.015, 0.05, 0.50, 1.0 ppm) on toxicity of dietary lead (0 and 200 ppm) in the young male rat indicated that selenium was mildly protective against the toxic effects of lead, but only up to 0.50 ppm selenium. At the excess selenium dietary level an exaggeration of lead toxicity was observed. Criteria employed to judge the effects of dietary selenium on lead toxicity included tissue lead concentration and urinary delta-aminolevulinic acid excretion. One exception to the exaggeration effect of excess selenium on lead toxicity was the protective effect of selenium on liver delta-aminolevulinic acid dehydratase activity. Since lead depressed kidney selenium concentration, lead may act as an antagonist to selenium metabolism.     

CNS oxygen toxicity in the rat: role of ambient illumination

The effect of ambient illumination on sensitivity to CNS oxygen toxicity was studied in awake male rats. Continuous recording of the EEG was obtained with chronically implanted cortical electrodes. The appearance of the electrical discharges in the EEG was used as an end point for CNS oxygen toxicity. It was found that sensitivity to CNS oxygen toxicity was inversely related to the level of ambient light illumination. The latent period for appearance of the electrical discharges was significantly shorter in darkness than in light over most of the oxygen pressures. Rats with severely depressed retinal function were as sensitive to oxygen at high pressure as normal rats in darkness, demonstrating the importance of visual input in the modulation of sensitivity to CNS oxygen toxicity.     

Influence of dietary zinc on lead toxicity in the rat.

An investigation of the influence of dietary zinc (8, 35, 200 ppm) on the toxicity of dietary lead (0, 50, 200 ppm) in the young male rat in a seven week period indicated that as dietary zinc increased, the severity of lead toxicity decreased. Evidence included decreased lead concentration in blood, liver, kidneys, and tibias; decreased excretion of urinary delta-aminolevulinic acid; decreased accumulation of free erythrocyte porphyrins; decreased inhibition of kidney delta-aminolevulinic acid dehydrase activity; and a decrease in apparent lead absorption. Infected zinc did not afford protection against lead toxicity. The data indicate that the protective effect of zinc on lead toxicity is largely mediated by an inhibition of lead absorption at the intestinal level.     

Sub-acute and sub-chronic toxicity ofmono-2-ethylhexyl phthalate in the rat

Groups of six male Sprague-Dawley rats were administered single oral doses of mono-2-ethylhexyl phthalate (MEHP) at 50, 100 or 200 mg/kg or di-2-ethylhexyl phthalate (DEHP) at 2,000 mg/kg in 2% gum acacia and were observed clinically for seven days. Body weight and food consumption were not affected by treatment. The liver weight increased in the groups receiving 100 mg or 200 mg mono-2-ethylhexyl phthalate and 2,000 mg diethylhexyl phthalate. Hepatic microsomal aniline hydroxylase activity was not altered by treatment.In a subsequent 28-day experiment, groups of ten weanling Sprague Dawley rats were fed diets containing 0, 25, 100, 400, 1,600 or 6,400 ppm of mono-2-ethylhexyl phthalate. Decreased growth rate occurred in the group receiving the highest dose level. Increased heart and liver weights were observed in animals from the 1,600 and 6,400 ppm groups. Minor alterations in serum biochemical values included decreased SDH and calcium levels, and elevated alkaline phosphatase activity in some treated groups. A mild reduction in red cells saturation and hematocrit was noted in some groups.In 3-month and 6-month feeding studies, groups of ten male and female weanling Sprague-Dawley rats were fed diets containing 1, 5, 25, 125 or 625 ppm of mono-2-ethylhexyl phthalate. Growth rate and food consumption were not affected at any dose level or time interval. Relative organ weights of rats of both sexes were not altered in the 3-month period, but the liver weights of female rats in the 6-month experiment were increased. Changes in clinical chemistry and hematological values were mild. These included lower LDH, SGOT, hemoglobin, and hematocrit values in male rats at the 3-month period and reduced potassium content at the 6-month period. Histological changes were mild in both male and female rats at both time intervals. Treatment-related lesions were found in the liver, heart, and adrenals. Alteration in the liver consisted of midzonal and periportal eosinophilic cytoplasmic inclusions and vacuolations with isolated binucleated and necrotic hepatocytes. There was a mild enlargement of myocardial nuclei and segmental deregistration of myocardial striations in test animals. The adrenal glands exhibited vacuolation of the zona fasciculata which was less severe in the 6-month period than the 3-month counterpart. In conclusion, mono-2-ethylhexyl phthalate is similar to its parent compound diethylhexyl phthalate in that it possesses a low order of oral toxicity in rats.