染料木素对大鼠生殖毒性的实验研究 (Ⅰ)一般生殖毒性

目的为保证染料木素临床用药的安全,评价其生殖毒性.方法16,160,480 mg/(kg·d)染料木素分别连续ig雄、雌性大鼠60 d,14 d后合笼,雄性大鼠给药至交配结束,雌性大鼠给药至妊娠第17天,观察染料木素对大鼠的受胎能力、生殖系统及子代的影响.结果染料木素480 mg/(kg·d)引起亲代雄性大鼠精子活动度下降,但未发现睾丸病变,也未影响雄鼠生殖能力;同时使雌鼠妊娠期体重增长明显低于其他组(P＜0.01),但未影响胚胎形成、仔鼠生长发育.160 mg/(kg·d)剂量对亲代和子代未引起明显的异常.结论染料木素160 mg/(kg·d)对雌、雄性大鼠无一般生殖毒性作用.     

双酚A生殖毒性及胚胎毒性的研究进展

通过对双酚A的生殖毒性,包括雄性生殖毒性、双酚A雄性生殖毒性机制和雌性生殖毒性;对双酚A的胚胎毒性的研究,涉及双酚A对雌鼠的胚胎毒性和双酚A对子一代雄鼠的遗传毒性;为临床建立有效的预防及治疗体系将具有极其重要意义。     

丹酚酸B注射剂的胚胎-胎仔发育毒性与遗传毒性

目的:研究丹酚酸B注射剂的生殖毒性及遗传毒性。方法:生殖毒性方面研究了丹酚酸B注射剂对SD大鼠胚胎-胎仔发育毒性的影响,于SD大鼠妊娠第6～15天分别连续静脉注射给予29、120、480 mg/(kg·d)的丹酚酸B注射剂,于妊娠第20天剖检,分析其生殖毒性。分别采用Ames试验、中国仓鼠肺细胞(CHL)染色体畸变试验、小鼠骨髓微核试验,观察丹酚酸B注射剂的遗传毒性。结果:胚胎-胎仔发育毒性试验中,丹酚酸B注射剂各剂量组的孕鼠均未出现明显毒性反应,中、高剂量的丹酚酸B注射剂会影响胎鼠发育。遗传毒性的Ames试验、CHL试验和微核试验均为阴性。结论:480 mg/(kg·d)及以下剂量的丹酚酸B注射剂对孕鼠无母体毒性作用。29 mg/(kg·d)的丹酚酸B注射剂对胚胎-胎仔发育无毒性;丹酚酸B注射剂未见明显遗传毒性。     

健脾生血颗粒对大鼠生育力与早期胚胎发育毒性的影响

目的评价健脾生血颗粒对大鼠生殖能力及早期胚胎发育的影响。方法将176只SD大鼠按性别分层,采用随机数字表法分为对照组及健脾生血颗粒低、中、高剂量组,分别以健脾生血颗粒0、1.16、3.48、5.80 g/(kg·d)给予雌鼠2周及雄鼠4周连续灌胃给药后,雌雄大鼠以1∶1合笼,雌鼠持续给药至妊娠第7天,雄鼠持续给药至剖检前,雄鼠整个给药周期为59~63天。剖检所有亲代动物,观察亲代动物体征形态,检查组织病理情况进行一般毒性检测;称重睾丸、附睾,计数附睾尾精子数并行精子活力检查检测生殖力毒性;计数黄体、活胎、死胎、吸收胎并计算着床数以观察早期胚胎发育毒性。结果 (1)一般毒性:健脾生血颗粒高剂量组雄鼠体重增长减缓。中低剂量组则无异常;(2)生育力毒性:健脾生血颗粒各剂量对雄鼠睾丸、附睾及附睾尾精子数量均无明显影响;(3)早期胚胎发育毒性:健脾生血颗粒各剂量组对早期胚胎形成未见明显影响。结论健脾生血颗粒一般毒性方面可能存在一定的胃肠毒性作用,未见毒性反应剂量为3.48 g/(kg·d)。健脾生血颗粒各剂量组均未见明显生育力及早期胚胎发育毒性反应。     

卡瓦胡椒水提取物不影响大鼠的肝功能

为研究卡瓦胡椒Piper methysticumForst.f.水提取物对肝功能的影响,作者进行了以下试验。将干燥卡瓦胡椒根于水中超声提取2次,每次20 min。提取液离心,上清液冷冻,制成干粉备用。雄性 SD 大鼠随机分为6组,4个给药组分别给予卡瓦内酯类200mg/(kg·d)(2或4周)和500 mg/(kg·d)     

Adenine生殖毒性系列研究-ⅠAdenine制作雄性Wistar大鼠不育症动物模型最佳时相的小样本研究

目的探讨阿拉伯胶助溶后的Adenine对Wistar大鼠生殖毒性的时效关系.方法将Adenine按500mg/mL浓度配制,按与Adenine 110比例加入阿拉伯胶作为助溶剂,1mL/kg·d-1剂量灌胃,每3天处死1组,做精子质量分析、用放免法检测性激素的变化,并对时效关系进行了观察.结果精子活动率及密度随给药时间延长呈下降趋势,在给药后第15天精子活动率呈显著性差异;睾酮(T)呈进行性下降,给药后前者第3天、后者第12天全部即出现显著性差异,FSH呈进行性上升,第9天出现显著性差异,第12天秩次最高.结论初步推定将Adenine按500mg/mL浓度配制,并加助溶剂后,1mL/kg·d-1剂量Wistar大鼠灌胃12天为其生殖毒性反映最佳时效,也可能为该给药剂量雄性大鼠不育症模型的最佳时相.     

新药用资源菠萝叶小鼠一般生殖毒性的研究

目的：对菠萝叶小鼠的一般生殖毒性进行研究,有助于更好的评价该植物的药用价值。方法：分别灌胃给予成年雄性和雌性小鼠菠萝叶,然后合笼进行交配。对于交配成功的雌鼠继续饲养。分别对孕鼠的妊娠、胎鼠的发育及生产的子代小鼠的情况进行实验观察。结果：菠萝叶除了大剂量（4 g·kg-1）对亲本雄性鼠体重有一定降低外,对其它各项指标均无明显影响。对孕鼠及其子代小鼠均未见有明显影响。结论：提示菠萝叶对小鼠一般生殖功能无明显毒性。     

染料木黄酮在雌雄大鼠体内的药动学

 目的观察染料木黄酮(genistein)在雌、雄大鼠体内的药动学差异。方法大鼠ig给予9mg·kg^-1染料木黄酮,用反相高效液相色谱法测定不同时间大鼠血浆中原型药物、β-葡萄糖醛酸结合型药物及组织器官中药物的浓度。结果药物在卵巢和子宫中的分布显著高于睾丸,在其他组织器官内的分布未观测到明显的雌雄差异。雌性大鼠的AUC,ρ_max和t_1/2分别为1.120 mg·h·L^-1,0.167mg·L^-1和5.767h。而雄性大鼠的AUC,ρ_max和t_1/2分别为0.592mg·h·L^-1,0.106mg·L^-1和4.486h。雌性大鼠血浆中葡萄糖醛酸结合形染料木黄酮浓度高于雄性大鼠。结论染料木黄酮在雌雄大鼠性器官中的分布具有差异显著;与雄性大鼠相比,雌性大鼠对染料木黄酮的吸收多、葡萄糖醛酸结合量高,使染料木黄酮的半衰期延长。     

微核试验和彗星试验检测朱砂的遗传毒性

目的:研究朱砂对大小鼠染色体的损伤作用,比较短期给药与长期给药对遗传毒性检出的影响,探讨结合生殖毒性Ⅰ段试验进行遗传毒性研究的可行性。方法:18只小鼠分3组灌胃给药10,5.02,.5 g.kg-1(分别相当于人临床最高等效剂量约100,50,25倍)朱砂悬浊液,2 d后处死;结合生殖毒性Ⅰ段大鼠(每组6只)连续灌胃给药1.0,0.3,0.1 g.kg-1(分别相当于人临床最高等效剂量的20,6.4,2.0倍),雄性42 d以上,交配成功后处死;雌性20 d以上,妊娠第15天处死,取骨髓细胞做微核试验和彗星试验。结果:小鼠各剂量组灌胃给药的微核率分别为0.175%,0.108%,0.092%,与阴性对照组比较差异有显著意义,但彗星试验结果阴性。结合生殖毒性Ⅰ段试验的微核试验中雄性和雌性大鼠的微核率与阴性对照组比较,差异无显著意义,但有随剂量增高而增高的趋势;而彗星试验结果显示雄性的中、高剂量和雌性的高剂量的拖尾阳性率为27.6%,42.8%,22.3%,与阴性对照组比较,差异有显著和极显著意义。结论:①朱砂短期内大剂量灌胃给药或长期小剂量给药可能引起染色体损伤;②利用生殖毒性Ⅰ段试验多次给药后取材做微核试验和彗星试验在方法上是可行的,在剂量设计上更符合中药长期低剂量给药方式;③微核试验和彗星试验的组合在评价药物的体内遗传毒性中具有互补性。     

合成冰片对小鼠一般生殖毒性研究

[目的]观察合成冰片对小鼠生殖能力的影响.[方法]ICR小鼠,随机分为正常对照组、合成冰片高中低剂量组,交配前雄鼠连续给药63 d,雌鼠连续给药14 d,雌鼠连续给药至交配成功后6d,雄鼠交配后处死,观察对雌雄动物一般情况和生育力等的影响.[结果]合成冰片高剂量（1.5 g/kg,约相当于药典推荐临床剂量300倍）组雄鼠生育率低于正常对照组,给药期间体质量下降.各组雌鼠受孕率、吸收胎及死胎率、活胎率均无显著差异.高剂量组F1代出生当天、21、28 d生长指数低于正常对照组.各组亲代雄鼠睾丸及附睾质量、精子计数、精子活力及精子畸形率各组比较均无显著性差异,睾丸组织形态学观察未见异常.[结论]在本实验条件下,合成冰片灌胃小鼠一般生殖毒性无作用剂量为0.75g/kg.1.5g/kg合成冰片可降低雄性小鼠体质量和生育率,降低F1代小鼠生长指数.     

昆明山海棠胶囊对小鼠的生殖毒性研究

目的:探讨昆明山海棠胶囊的生殖系统毒性.方法:根据卫生部<中药新药研究指南>,进行该制剂的特殊毒理实验研究.结果:显性致死试验阳性;雌鼠均不能受孕;精子畸形率显著增高,随剂量增加而精子畸形率增高;对孕鼠重量、活胎重量及平均胎仔数等各项指标均无影响.结论:昆明山海棠胶囊具有低-中度的遗传毒性和一般生殖毒性,而无胚胎毒性.     

昆明山海棠胶囊对小鼠的生殖毒性研究

目的：探讨昆明山海棠胶囊的生殖系统毒性.方法：根据卫生部《中药新药研究指南》,进行该制剂的特殊毒理实验研究.结果：显性致死试验阳性;雌鼠均不能受孕;精子畸形率显著增高,随剂量增加而精子畸形率增高;对孕鼠重量、活胎重量及平均胎仔数等各项指标均无影响.结论：昆明山海棠胶囊具有低-中度的遗传毒性和一般生殖毒性,而无胚胎毒性.     

The reproductive toxicity of saponins isolated from Cortex Albiziae in female mice

Saponin frsom Cortex Albiziae(SCA) are extensively used in the clinical treatment of tumor and depression. However, SCA may cause several adverse effects, including reproductive toxicity. The present study was designed to assess the mechanism by which SCA cause reproductive toxicity in female mice. The general reproductive toxicity testing was accomplished in female Kunming mice. The animals were divided into four groups: three groups that were treated by oral gavage with 135, 270, and 540 mg·kg-1·d-1 of SCA prepared in physiological saline, respectively, and one vehicle control group that was treated with physiological saline only. The gestational toxicity tests were conducted at 540 mg·kg-1·d-1. The general reproductive toxicity results showed that the pregnancy rate of the SCA-treated group decreased with the pregnancy rate being decreased by 70% at 540 mg·kg-1·d-1. SCA elicited maternal toxicity in the ovary and the uterus, but no fetal toxicity or teratogenicity was observed. The rates of implantation in the early, middle, and late pregnancy were all decreased, with stillbirths and maternal deaths being observed. Histopathological changes showed that SCA adversely affected the ovary and the uterus. In conclusion, SCA-induced reproductive toxicity in female mice is most likely caused by its damage to the ovary and the uterus.     

Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds

ObjectiveIn traditional medicine, the seeds of Thai Mucuna pruriens (T-MP) are used to treat male dysuria and are believed to enhance fertility. However, information pertaining to the toxicity of T-MP and its interaction with other properties is limited. This study was thus conducted to evaluate the antioxidant capacity and subacute toxicity of T-MP in the reproductive system.MethodsTotal phenolic content and antioxidant capacity of T-MP seed extract were determined using total phenolic content, 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Male and female adult rats were treated orally with T-MP at a dosage of 150 or 300 mg/kg body weight for 14 consecutive days. Sex hormones and functional parameters in the liver and kidney were evaluated. Histopathology of all tissue was conducted using Masson’s trichrome staining. Sperm parameters, including concentration, morphology, acrosome reaction status and DNA damage, were also examined. Expression of tyrosine phosphorylated protein (TyrPho), androgen receptor and A-kinase-anchoring protein 4 (AKAP4) were investigated using the Western blot technique.ResultsT-MP seed extract contained phenolic compounds and exhibited high antioxidant capacity with no toxicity at the tested doses. It did not affect liver or kidney function parameters in the male rats, but increased estradiol, aspartate aminotransferase and alanine aminotransferase levels in the females. Additionally, it decreased serum progesterone and alkaline phosphatase levels in female rats. Serum and intratesticular testosterone levels were significantly lower in male rats that received a high dosage of T-MP. Histopathological changes were not observed in any tissue treated with T-MP. T-MP also significantly increased sperm concentration (but did not affect sperm parameters), and enhanced testicular TyrPho protein and androgen receptor and expression of AKAP4 in sperms.ConclusionT-MP seed extract exhibited antioxidant capacity and was not harmful to reproductive tissues. It also had a phytoestrogenic effect on females and increased the expression of testicular and sperm markers of male fertility.     

Screening for reproductive toxicity in rats for a decoction of Himathanthus sucuuba stem bark.

In order to evaluate the toxic potential of a Himathanthus sucuuba stem bark decoction, pregnant rats were treated from day 6 to day 15 of pregnancy with the decoction (40 mg per rat, twice a day) or distilled water (1.0 ml, twice a day) by gastric intubation. Half of the animals were killed on day 20 of pregnancy with the other half allowed to deliver. Maternal and fetal data suggest low reproductive toxicity and teratogenic potentiality and suggest that the beverage may be safe for human use in the treatment of gastritis and haemorrhoids.     

半夏茯苓汤不同方法炮制半夏对小鼠生殖毒性的作用

目的探讨临床常用于治疗妊娠恶阻的复方—半夏茯苓汤中,半夏不同炮制方法(生半夏、姜半夏、法半夏)对妊娠母鼠的肝肾毒性、致畸胎、死胎的药物不良反应的生殖毒性。方法选取临床治疗妊娠恶阻应用频率最高的复方—半夏茯苓汤进行不同炮制半夏生殖毒性的实验研究。实验中建立阳性对照组(即丝裂霉素C组),空白对照组(生理盐水组),实验组(半夏茯苓汤中所用半夏分别为生半夏、姜半夏、法半夏3组)等,对生殖毒性进行探讨。结果通过SPSS 18.0进行统计学分析,半夏茯苓汤中,生半夏组的致畸胎率(5.38%)、致死胎率(4.30%)均高于姜半夏(4.13%,4.13%)、法半夏组(3.03%,2.27%),具有统计学意义(P<0.05)。结论半夏茯苓汤用法半夏治疗孕妇妊娠呕吐最为安全,孕妇需慎用未经炮制的生半夏的复方。     

Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats

ObjectiveCyclophosphamide (CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract (AE) and methanolic extract (ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats.MethodsIn addition to a normal control (group 1), drugs or vehicles were administered orally to seven groups (n = 5) of rats that had already received 4-weeks of pre-treatment with CP (5 mg/[kg·d], per oral administration); group 2 received CP + distilled water (10 mL/[kg·d]); group 3 received CP + 5% tween 80 (10 mL/[kg·d]); group 4 received CP + clomiphene citrate (0.25 mg/[kg·d]); groups 5 and 6 received CP + AE (50 and 100 mg/[kg·d]) and groups 7 and 8 received CP + ME (50 and 100 mg/[kg·d]). Animals were sacrificed on day 15, and body and sexual organ weights, sperm characteristics, testosterone level and testicular histology were evaluated.ResultsThe CP-treated group showed a significant reduction (P < 0.001) in the body and seminal vesicle weights, testosterone level, sperm count, sperm motility and sperm viability, but elevated (P < 0.001) sperm morphological abnormalities and testicular structure alterations, compared to the control group. Interestingly, these detrimental effects of CP were reversed by treatment with H. odoratissimum extracts. For instance, both extracts and all doses of H. odoratissimum significantly increased the sperm count (P < 0.001), sperm motility (AE, 50 mg/kg, P < 0.05; ME, 50 and 100 mg/kg, P < 0.05) and sperm viability (AE, 50 mg/kg, P < 0.001; ME, 50 and 100 mg/kg, P < 0.001) compared to the CP group. H. odoratissimum also improved plasmatic and intratesticular testosterone levels and prevented histological alterations of the testes.ConclusionH. odoratissimum might be considered as an alternative drug to alleviate/prevent reproductive damage in cancer patients receiving CP chemotherapy.     

Evaluation of the toxicity of Solanum lycocarpum in the reproductive system of male mice and rats

Powdered Solanum lycocarpum fruit is commonly used to treat diabetes, but apparently no studies have been conducted to evaluate potential adverse side effects. In the present paper the toxic effect of S. lycocarpum was evaluated in adult male Wistar rats and Swiss mice. The administration of an aqueous extract prepared using a powder obtained from the S. lycocarpum fruit at two different dose levels (60 mg/15 ml and 120 mg/15 ml distilled water for rats and 30 mg/15 ml and 60 mg/15 ml distilled water for mice, twice daily for 5 days in each case) did not produce body weight variations in either species although a significant weight change was observed in some organs. Significant weight loss was observed only in the ventral prostate of mice receiving the high dose treatment. These results suggest a toxic effect of S. lycocarpum on the male reproductive system of the Swiss mouse, with possible antiandrogenic activity, but there was no apparent antifertility activity in rats at the doses given.