The mechanism of testicular toxicity of cadmium is poorly understood. Previous studies focusing on cadmium-related changes in testicular histopathology have implicated testicular blood vessel damage as the main cause of cadmium toxicity. To further explore the toxic effects of cadmium on testis, we isolated and cultured rat Leydig cells, exposed to 10, 20, and 40 microM of cadmium chloride (base doses). After 24 h of exposure, cells and supernatants were harvested to examine cytotoxicity and genotoxicity of cadmium. The results show that both cell viability and concentration of testosterone excretion in primary Leydig cells are significantly lower in cadmium-exposed groups compared to the controls. Changes in testosterone excretion with human chorionic gonadotropin (hCG) stimulation is especially profound. The contents of malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-Px) in exposed groups are significantly higher than those in the control group, but the activity of superoxide dismutase (SOD) is lower. The number of cells with DNA single strand breaks and the levels of cellular DNA damage in all three exposure groups are significantly higher than in controls. These results indicate that cadmium is directly toxic to primary Leydig cells, and that the decreased percentage of normal cells and the increased level of DNA damage in cadmium-exposed Leydig cells may be responsible for decreased testosterone secretion.
Objective Time-course of gene expression of metallothionein (MT1 and MT2) in kidney conex from mice were measured.Methods Following an initial high CdMT dose and four subsequent low doses (50+4×25μg/kg) administered subcutaneously at an interval of 2h,with semi-quantitative RT-PCR.Results The MTI gene expression level was higher at 12 h and returned its basal level at 168h after first injection.The MT2 gene expression level was significantly higher at 12 and 24h and also returned its basal level at 168h.The MT1 and MT2 gene expression level reached to the maximum at 24h.Conclusion MT1 and MT2 genes in mice's kidney cortex from mice could be induced by multiple short-interval CdMT injections.Time course of MT1 and MT2 gene expression was parallel.
目的探讨胃癌的生物学特性及与临床之间的关系.方法对1034例各期、各个部位的胃癌的临床及病理资料进行回顾性分析.结果早期胃癌148例,占总数的14.3%; 胃体和胃底部的胃癌淋巴结转移率明显高于其它部位的胃癌(P<0.0001); 肿瘤直径大的胃癌分化差(P=0.004)、浸润深(P<0.0001),淋巴结转移率也较高(P<0.01).浸润深度较深的胃癌患者平均年龄大于浸润深度较浅的患者(P=0.003),分化差的患者平均年龄低于分化好的患者(P<0.0001).女性患者的肿瘤相当一部分位于胃的近端,男性则以位于胃的远端为多见(P<0.001); 女性患者肿瘤分化差的比例高于男性(P<0.001),淋巴结转移率>30%以上者也比男性高(P=0.01).多因素线性多元回归分析发现,肿瘤部位(P=0.003)、直径(P<0.0001)、浸润深度(P<0.0001)及分化程度(P<0.001)与淋巴结转移密切相关,女性患者较男性更易发生淋巴结转移(P<0.001),其中决定淋巴结转移最重要的因素是肿瘤浸润胃壁的深度.全胃切除术清扫的淋巴结数最多,其次为远端胃大部切除术; 术后并发症发生率最高的手术是经腹近端胃大部切除术(17%).结论为降低术后复发,对各期胃癌手术时均应进行淋巴结的清扫.
Objective To explore the time course of the renal impacts inducedby multiple short-interval injections of cadmium-metallothionein (CdMT) in female mice.Methods The mice were given with an initial high dose and with four subsequent low doses (0.05+4×0.025 mg/kg) subcutaneously at 2 h intervals. The excretion of cadmium, calcium and protein in urine and changes of calcium and level in kidney cortex were studied following the first injection. Results The calcium level in kidney cortex were significantly higher at 24 and 336 h after the first injection. The excretion of calcium and protein in urine appeared to be markedly increased to a maxiumal value at 168 h and kept until 336 h. Conclusion Marked nephrotoxic effects after multiple short-interval CdMT injections were shown with rather long duration. The disturbance of calcium homeostasis might be one of the possible mechanisms of such renal impacts.
[Objective] The aim of this study was to investigate the susceptibility of type-2 diabetic mice (Umea ob/ob mice) to cadmium-metallothionein (CdMT)-induced nephrotoxicity. [Methods] 18 of female ob/ob mice and 18 of their lean litter mates (normal mice) were randomly divided into three groups for each type,and administered subcutaneously with CdMT 5 times in short interval. The different doses of CdMT were given to both types of mice based on the ratio of kidney weight to body weight in order to reach the same level of cadmium in renal cortex. [Results] The significant increase in NAG and calcium in urine and in renal cortex was found at the lower level of cadmium in renal cortex in ob/ob mice than in normal mice. [Conclusion] The authors concluded that ob/ob mice were more susceptible to CdMT-induced renal damage.
本文应用高压液相-电化学(HPLC-EC)技术对52名男性不育患者精子DNA中8-羟基脱氧鸟苷(8-OHdG)进行测定,同时检测精液量、精子密度、精子活率、正常形态精子率,及头部精子畸形等精液参数,并进行相关性分析.结果显示,当精子DNA中8-OHdG超过10.50时,其头部畸形率明显增加.精子DNA中8-OHdG与精液量(r=-0.47,P<0.001)、正常形态精子率(r=-0.36,P<0.01)成一定的负相关,且与头部畸形精子率成正相关(r=0.69,P<0.001).结果提示,精子DNA中8-OHdG与精液质量存在一定的相关性,表明精液质量的下降与精子DNA的损伤存在一定联系,而内源及外源性活性氧是可能的原因之一,其可能的机制尚需进一步研究.
The aim of this study was to explore the ability of induced expression of metallothionein genes related to the susceptibility of type 2 diabetic mice (ob/ob mice) to cadmium metallothionein(CdMT) induced nephrotoxicity. With semi quantitative RT PCR,gene expressions of MT1 and MT2 induced by the same cadmium level in the renal cortex of type 2 diabetic mice and their lean litter mates (normal mice) were studied. Gene expressions of MT1 and MT2 in the renal cortex of ob/ob mice could not be induced obviously by CdMT. However they could be induced significantly in that of normal mice. [Conclusion] The authors concluded that there were some relationships between the possible mechanisms of the susceptibility of type 2 diabetic mice to CdMT induced nephrotoxicity and the lower ability of induced expressions of MT1 and MT2 genes in the renal cortex.
Objective To explore the changes of metallothionein(MT) gene expression induced by multiple short interval injections of cadmium metallothionein(CdMT) in mice. Methods With semi quantitative RT PCR,gene expression of MT1 and MT2 in renal cortex were studied following an initial CdMT dose and four subsequent doses administered subcutaneously at an interval of 2 hrs. Results MT1 and MT2 gene expression in renal cortex increased with the increasing of CdMT dose.At the dose of 0.60 mg/kg,MT1 and MT2 gene expression in renal cortex(1.60±0.12 and 1.44±0.05,respectively) were significantly higher than those of controls (1.22± 0.16 and 0.92± 0.12, P 0.05, P 0.01 respectively).MT1 and MT2 gene expression in renal cortex were correlated to Cd level in renal cortex( r =0.72 and r =0.71 respectively, P 0.01). Conclusion Both MT1 and MT2 gene expression in renal cortex could be obviously induced by cadmium.There were similar changing tendencies between MT1 and MT2 gene expression in renal cortex.
<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">为研究镉对雄性生育功能的影响 ,将大鼠皮下注射氯化镉染毒 5周。雄鼠染毒结束后与正常成年雌鼠按 1∶2合笼交配 1周 ,于妊娠第 2 1天处死雌鼠 ,检查雌鼠的黄体数 ,胎鼠的性别、体重、身长和尾长。结果显示 ,随着染毒剂量的增高 ,各组参与交配的雄鼠数显著下降 (P <0 .0 5 ) ,交配成功的雌鼠数也显著降低 (P <0 .0 1)。低剂量组有活胎的孕鼠数明显低于对照组 (P >0 .0 5 ) ,中、高剂量组孕鼠无活胎。 2组胎鼠的平均体重、身长、尾长和胎鼠性别比例与对照组比较无显著差异(P >0 .0 5 )。 2组胎鼠未发现明显的骨路畸形。这表明镉可明显影响雄性生育功能 ,但对于成功受孕后的胎鼠影响不明显</span>
Objective To explore the acute nephrotoxic impact caused by multipleshort-interval injections of cadmium-metallothionein (CdMT) in mice. Methods Theurinary excretion of calcium and protein and changes of calcium and cadmium in kidneycortex were studied following an initial CdMT dose and four subsequent dosesadministered subcutaneously at 2 h intervals. Results The dose-related increasesin calcium and cadmium level in kidney cortex and excretion of calcium and proteinin urine were found. The calcium and cadmium level in kidney cortex are significantlyhigher than those in liver at 64 h after the last treatment of CdMT. Conclusion Theresults indicate that nephrotoxic impact can be induced by multiple short-intervalCdMT injections and the disturbances of calcium metabolism may be one of the possibletoxicological mechanisms.
[目的] 探讨双酚A对大鼠的胚胎毒性作用.[方法] 将交配成功的雌鼠在整个妊娠期每天灌胃染毒.观察双酚A对妊娠雌鼠及胎鼠等的影响.[结果] 染毒剂量为每天20mg/kg时,胎鼠体重明显下降.随着染毒剂量的增加雄仔鼠体重逐渐降低,染毒剂量达每天200mg/kg时,平均窝仔数明显减少,胎鼠身长和尾长也发生显著性的改变.[结论] 双酚A具有一定的胚胎毒性作用.
双酚A,又名4-二羟基二苯基丙烷,属低毒性,是制造聚碳酸脂、环氧树脂、聚酚酚树脂及聚氧树脂的重要原料.近年来有报道表明其具有雌激素样作用,影响生殖功能[1,2].睾丸Leyding细胞是合成和分泌睾酮的细胞,并具有高度的调节性,本实验在建立睾丸Leyding细胞离体原代培养的基础上,对双酚A的Leyding细胞毒性进行了初步的探讨.
精液中的多种微量元素可能与男性生殖能力有关[1].有些学者认为,精液中锌、铜、镁、钙、铁和硒等元素对男性生殖功能均有较大的影响[2].镉为有毒的人体非必需元素,除了直接的毒作用外,它与其他微量元素间的相互竞争作用,可能导致其他微量元素含量的变化,进而对机体产生相应的影响.为了解镉接触对精浆微量元素含量的影响, 我们对镉接触工人的精液进行了分析.
Epidemiological surveys and animal experiments have shown that 2-bromopropane induces oligozoospermia in exposed workers and inhibits spermatogensis in laboratory animals. However, the mechanism by which 2-bromopropane exerts its effects is unknown. To this end, we examined the formation of testosterone by the Leydig cells and their survival of these cells in the presence of different concentrations of 2-bromopropane in vitro. Leydig cells were isolated following vascular perfusion, enzymatic dissociation and Percoll gradient centrifugation techniques. The cells were cultured in culture dishes. After 8 h, different cultures were exposed to 2-bromopropane at concentrations of 0.01 mmol/L, 0.10 mmol/L and 1.00 mmol/L. In order to stimulate Leydig cells to secrete testosterone, human chorionic gonadotropin (hCG) was also added. Cell viability was determined using the trypan blue dye exclusion test and cell numbers were counted by hemocytometer. Testosterone secretion was detected by radioimmunoassay. The cell viability decreased after exposure to 2-bromopropane in a dose-dependent way, but no morphological change was observed. The cell number decreased in the 2-bromopropane-treated cultures. The secretion of testosterone did not manifest defectable changes in the culture treated with 0.10 mmol/L and 0.01 mmol/L of 2-bromopropane; however, it decreased significantly (P < 0.02) in the presence of 1.00 mmol/L. Therefore, our results strongly suggest that 2-bromopropane may exert its cytotoxic effects on Leydig cells in vitro. We speculate that the decrease in the numbers of Leydig cells caused by 2-bromopropane was mediated by a feedback mechanism resulting from a lower testosterone concentration.
本实验采用某沙漠地区沙漠尘给大鼠气管内注入染尘。实验分石英、沙漠尘高剂量组(分别50mg/只)和低剂量组(分别25mg/只)及空白对照组。大鼠染尘后1、3、6、9和12个月分别处死,测定肺重及全肺胶原蛋白、总脂和类脂含量,并作病理组织学检查。结果表明:沙漠尘对肺重及组织生化指标有一定的作用,且粉尘在肺组织中长期沉积,并引起以异物巨细胞为主的反应,与石英尘相比,未见明显矽结节纤维化改变。作者认为,沙漠尘致纤维化能力弱。