Role of curcumin on chloroquine phosphate-induced reproductive toxicity

The present study was conducted to screen the efficacy of curcumin against chloroquine phosphate (CQ)-induced reproductive toxicity in adult male Swiss albino mice. Animals were given oral doses of 100, 200, 300?mg/kg body weight (b.w.), and high dose of CQ (300?mg/kg b.w.) + curcumin (80?mg/kg b.w.) for 45 days. Animals of the withdrawal group were given high dose of CQ (300?mg/kg b.w.) for 45 days and, at day 46, were kept for another 45 days. Effects were observed on some key enzymes, such as alkaline phosphatase, which was found to be decreased, whereas acid phosphatase was increased and succinate dehydrogenase and adenosine triphosphatase were decreased. Oxidative parameters, such as superoxide dismutase declined, whereas thiobarbituric acid-reactive substances were found to be elevated. Protein level was also decreased. Gravimetric indices were also recorded. Results obtained indicated adverse effects of CQ in a dose-dependent manner. The presence of curcumin with CQ alleviated its toxic effects. Hence, it can be concluded that curcumin has beneficial influences and appears able to ameliorate CQ toxicity.     

Evaluation of ameliorative effect of curcumin on imidacloprid‐induced male reproductive toxicity in wistar rats

This study was undertaken to investigate the toxic effects of imidacloprid (IM) on male reproductive system and ameliorative effect of curcumin (CMN) in male Wistar rats. For this purpose, IM (45 and 90 mg/kg, body weight) and CMN (100 mg/kg, body weight) were administered orally to the rats either alone or in combinations for a period of 28 days. At the end of experiment, male reproductive toxicity parameters (total sperm count and sperm abnormalities), testosterone level, steroidal enzymatic activity [3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17β‐HSD], and oxidative stress indicators were estimated in testis and plasma. IM treatments resulted in significant decrease (p < 0.05) in total epididymal sperm count, sperm motility, live sperm count, and increase (p < 0.05) in sperm abnormalities. Activities of gamma‐glutamyl transpeptidase, lactate dehydrogenase‐x, and sorbitol dehydrogenase were significantly increased (p < 0.05), while, 3β‐HSD and 17β‐HSD enzymatic activity along with testosterone concentration in testis and plasma were decreased significantly (p < 0.05) in IM‐treated rats. IM exposure resulted in significant increase (p < 0.05) in LPO and decrease (p < 0.05) in GSH level along with decreased activities of CAT, SOD, GPx, and GST. IM‐treated rats showed histopathological alterations in testis and epididymis. However, the reproductive toxicity parameters, oxidative stress indicators, and histopathological changes were minimized and functional restorations were noticed by co‐administration of CMN in IM‐treated rats. The results of this study suggest that IM‐induced male reproductive toxic effects could be ameliorated by CMN supplementation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1250–1263, 2016.     

Effect of hyperthermia on acute chloroquine toxicity in rabbits

The problem of sudden and unexpected death after the parenteral administration of a therapeutic dose of choloroquine in fibrile patients was investigated using rabbits. Hyperthermia was produced in both conscious and anaesthetized rabbits using a Megatherm Junior diathermy machine. Lead II of the electrocardiogram, respiration and blood pressure were monitored during slow i.v. injection of chloroquine. In hyperthermic rabbits, striking cardiac arrhythmias, circulatory collapse and death occured at a dose level $\text{1}\text{3}$ as great as in normal rabbits. Animals that had been heated and allowed to cool before the injection, tolerated $\text{2}\text{3}$ of the lethal dose for normal rabbits, and twice as much as the hyperthermic rabbits.     

Protective effect of Nigella sativa oil against acetamiprid induced reproductive toxicity in male rats

The present study was designed to investigate the adverse reproductive effects of acetamiprid, besides the possible protective role of Nigella sativa oil (NSO), as a potential antioxidant agent. Thirty-two male Wistar rats were allocated into four equal groups of eight, control (CRL), acetamiprid (ACMP, 27?mg/kg), Nigella sativa oil (NSO, 0.5?ml/kg) and in combination (ACMP?+?NSO). The experimental animals were dosed by gavage (5?days per week) for 45 consecutive days. Body weight gain, reproductive organs weights, sperm characteristics, testosterone, and thiobarbutiric acid-reactive substances (TBARS) levels were investigated. The obtained results showed that ACMP decreased significantly (p?p?p?p?相似文献   

含吲哚美辛固定式宫内节育器的生殖毒性研究

目的：应用健康未交配过昆明种小鼠对固定式宫内节育器进行生殖毒性研究.方法：观察不同剂量含吲哚美辛固定式宫内节育器对动物性功能、发情周期、交配行为、受孕、分娩、授乳和断乳的影响,以及对子代生长发育、幼鼠发病率、死亡率的影响和是否具有致畸性的作用.结果：在人体使用量的等效剂量下,该节育器未见引起明显的生殖毒性作用,而中、高剂量组对受试动物具有一定的生殖毒性作用.结论：含吲哚美辛固定式宫内节育器,在相对于人体剂量使用条件下对生殖过程无明显毒性作用.     

Effects of nanoparticle‐encapsulated curcumin on arsenic‐induced liver toxicity in rats

We investigated the therapeutic effectiveness of the nanoparticle‐encapsulated curcumin (CUR‐NP) against sodium arsenite‐induced hepatic oxidative damage in rats. The CUR‐NP prepared by emulsion technique was spherical in shape with an encapsulation efficiency of 86.5%. The particle size ranged between 120 and 140 nm with the mean particle size being 130.8 nm. Rats were divided into five groups of six each. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in group 2, however, they were administered, empty nanoparticles, curcumin (100 mg/kg bw) and CUR‐NP (100 mg/kg bw), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic increased the activities of serum alanine aminotransferase and aspartate aminotransferase and caused histological alterations in liver indicating hepatotoxicity. Arsenic increased lipid peroxidation, depleted reduced glutathione and decreased the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in liver. All these effects of arsenic were attenuated with both curcumin and CUR‐NP. However, the magnitude of amelioration was more pronounced with CUR‐NP. The results indicate that curcumin given in nano‐encapsulated form caused better amelioration than free curcumin. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 628–637, 2015.     

Mechanism of deltamethrin induced thymic and splenic toxicity in mice and its protection by piperine and curcumin: in vivo study

Deltamethrin (DLM) is a well-known pyrethroid insecticide which is widely used in the agriculture and home pest control due to restriction on the sale of organophosphate. DLM induced apoptosis is well known but its mechanism is still unclear. This study has been designed to find out its mechanism of apoptosis with the help of computational methods along with in vivo methods. The QikProp and ProTox results have shown that DLM has good oral absorption. The docking results reveal that DLM has a strong binding affinity toward the CD4, CD8, CD28 and CD45 receptors. Further, to understand the toxicity of DLM on lymphoid cells, a single dose of DLM (5?mg/kg, oral for seven days) has been administered to male Balb/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (caspase-3 activity, DNA fragmentation) have been assessed in thymic and splenic single cell suspensions. Lowering of body weight, cellularity and loss in cell viability have been observed in DLM treated mice. The significant increase in ROS and GSH depletion in spleen and thymus, indicate the possible involvement of oxidative stress. The spleen cells appear more susceptible to the adverse effects of DLM than thymus cells. Further, for the amelioration of its effect, two structurally different bioactive herbal extracts, piperine and curcumin have been evaluated and have shown the cytoprotective effect by inhibiting the apoptogenic signaling pathways induced by DLM.     

儿童过量服用磷酸氯喹/磷酸伯氨喹的毒性特征分析

目的分析儿童过量服用磷酸氯喹/磷酸伯氨喹后的毒性反应特征,为合理用药及毒性反应的防治提供参考。方法收集我院收治的39例过量服用磷酸氯喹/磷酸伯氨喹儿童的病历资料,对服用药物后出现毒性反应的时间、临床症状以及血常规、肝功能、肾功能、心电图等检测指标的变化情况进行分析。结果儿童服用过量磷酸氯喹/磷酸伯氨喹后约3.9 h出现毒性反应。毒性反应主要累及神经系统、消化系统、循环系统,发生率分别为76.92%、74.36%、53.85%,主要临床症状为头晕、头痛、腹痛、腹泻、心律失常、心悸等。结论儿童过量服用磷酸氯喹/磷酸伯氨喹后毒性反应发生率高,毒性反应严重,应予积极救治,并做好肝肾功能等指标的监测。     

Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice

To investigate the protective effect of testosterone propionate (TP) on reproductive toxicity caused by endosulfan in male mice, three group experiments were designed: the control group received 0 and 0, the endosulfan group received 0.8 and 0, and the endosulfan + TP group received 0.8 mg/kg/d endosulfan and 10 mg/kg/d TP, respectively. The results showed that TP significantly prevented the declines of concentration and motility rates in sperm, reduced the rate of sperm abnormalities in epididymis; and antagonized the decreases in spermatogenous cell and sperm numbers in testes induced by endosulfan. TP also decreased the numbers of cavities formed, prevented the decreases of plasma testosterone and androgen receptor (AR) mRNA in testicular tissue, alleviated the increase of LH induced by endosulfan. It is likely that TP relieve the reproductive toxicity by reversing the endosulfan‐induced decreases in testosterone secretion and AR expression that resulted from the alteration of Leydig cell function. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 142–153, 2016.     

姜黄素对软骨细胞氧化应激损伤的保护作用

目的：通过建立H2O2诱导软骨细胞损伤模型,观察姜黄素对软骨细胞的保护作用。方法体外培养SD大鼠关节软骨细胞,随机分为对照组、模型组（H2O2）、姜黄素低中高剂量剂量组（20、40、80μmol／L）。姜黄素与软骨细胞培养48 h后,加入H2O2,24 h后收集细胞,MTT和流式细胞仪测定细胞增殖能力,测定细胞超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）含量,Real－Time PCR和Western blot法检测细胞Nrf2 mRNA及其蛋白表达水平。结果与对照组比较,模型组软骨细胞存活率降低,具有分裂象的S期和G2／M期细胞明显减少;SOD、CAT含量降低,MDA含量增加,Nrf2 mRNA及其蛋白表达水平下调。经姜黄素预先处理,软骨细胞存活率升高,细胞增殖能力恢复,SOD、CAT含量升高,MDA含量降低,Nrf2 mRNA及其蛋白表达水平升高。随浓度升高变化更明显。结论姜黄素对软骨细胞氧化应激损伤有保护作用,可通过增强Nrf2表达实现。     

羟基脲对雄性大鼠的生殖毒性

目的观察羟基脲(HU)对雄性大鼠的生殖毒性。方法雄性大鼠分别腹腔注射HU×100、200和400mg·kg-1,连续10d。末次给药后分别于d9、d23处死动物。结果停药d9时,200、400mg·kg-1组不活动精子增加明显(P<0.05或P<0.01);停药d23时,各给药组睾丸脏/体比都明显下降(P<0.05或P<0.01);400mg·kg-1组附睾脏/体比下降明显(P<0.05),并且仍然有大量不活动精子(P<0.01);200、400mg·kg-1组精子计数明显减少(P<0.01);随给药浓度增加,各组精子畸形数量增加(P<0.01)。结论雄性大鼠连续10d腹腔注射羟基脲100mg·kg-1以上,对生殖系统产生明显毒性。     

Protective effects of curcumin on methylglyoxal-induced oxidative DNA damage and cell injury in human mononuclear cells

AIM: To examine the effect of curcumin on oxidative DNA damage and cell apoptosis and injury caused by the reaction of methylglyoxal(MG) with amino acids. METHODS: We used DNA strand breaks to examine the effect of curcumin on oxidative DNA damage. In addition, reactive oxygen species(ROS) formation occurs in MG-treated mononuclear cells, so the effect of curcumin on ROS generation was measured using 2',7'-dichlorofluorescin diacetate(DCF-DA) as the detection reagent. Moreover, the impact effects of curcumin on MG-induced cell apoptosis and ROS injury were analyzed by TUNEL and ELISA assay. The collagen I attachment ability of mononuclear cells was examined by trypan blue staining. RESULTS: Our results revealed that curcumin prevented MG/lysine-induced oxidative stress and DNA damage. Curcumin also inhibited MG-induced apoptosis and generation of ROS in mononuclear cells. MG-treated mononuclear cells displayed a lower degree of attachment to collagen (the major component of the vessel wall subendo-thelium), whereas cells pretreated with curcumin before MG treatment exhibited restored affinities for collagen. CONCLUSION: These results demonstrated that oxidative stress plays a role in MG-induced cell injury and alterations in attachment ability, and that curcumin blocks these effects by virtue of its antioxidant properties.     

化学物质生殖毒性替代方法的研究现状

科技发展和人类进步,促进3R理论发展,即减少、替代和优化试验动物的使用。因此,众多努力用于毒理学替代方法的研究。生殖和发育毒性检测中使用的动物数量最多,但因哺乳动物生殖周期的复杂性,生殖发育毒性替代方法的研究进展缓慢。胚胎干细胞、微团检测和全胚胎培养试验,以及非洲蟾蜍胚胎试验,可作为发育毒性的筛检方法。利用人生殖细胞体外模型进行生殖毒性研究是一个挑战。跨领域技术、传感器技术、(Q)SARs及各种组学技术的迅速发展,都将使生殖发育毒性替代方法的研究得到新的发展和突破。     

如何成功开展药物非临床生殖毒性试验

本文围绕如何成功开展药物非临床生殖毒性试验展开讨论,认为:①在大鼠生育力与早期胚胎发育毒性试验(Ⅰ段)中,应该选用年轻、性成熟的成年动物,雌性动物需未经产;雄鼠交配前给药期限超过9周比较稳妥;不建议利用医院使用的人类精子质量分析系统,人工镜检或动物精子分析系统都可行,后者较客观。②在胚胎-胎仔发育毒性试验(Ⅱ段)中,一般不建议采用从饲养场购买的孕兔开展研究;交配笼的使用有利于提高实验用兔的交配成功率。③在围产期毒性试验(Ⅲ段)中,受试物为生育调节和细胞毒性药物时,应该观察到F2代的行为,甚至F2代生育力和F3代的行为,以检测生殖毒性有可能的延续性;应避免F1代的兄妹(或姐弟)交配。④选择在易发情季节,挑选性成熟的动物,特别是在Ⅱ和Ⅲ段试验中选用有交配经验的雄性动物,是提高实验动物交配成功率的主要关键点。最好设立阳性对照组,增加激素水平的检测,如雌、雄激素等。适当增加与性功能、性活动有关的检测指标以及对于生殖相关的器官进行组织病理学检查。这些都是能够成功开展药物非临床生殖毒性试验的关键技术。     

生殖毒性试验的质量保证

生殖毒性试验是毒理学试验中最为复杂、繁琐,技术要求最高的试验,在药品非临床研究质量管理规范（GLP）和质量保证（QA）检查方面有其特殊性.现从实验室资质的确认、试验关键阶段的检查、研究资料和报告的审查、特殊评价项目的质量保证和现场检查等5个方面介绍生殖毒性试验质量保证的程序、要求和注意事项.     

Mercury vapor and female reproductive toxicity.

Epidemiological studies finding menstrual cycle abnormalities among women occupationally exposed to Hg degrees prompted us to investigate the mechanisms of reproductive toxicity of Hg degrees in the female rat. Nose-only Hg degrees vapor inhalation exposures were conducted on regularly cycling rats 80-90 days of age in dose-response and acute time-course studies, which have previously proven useful as a model to identify ovarian toxicants. Vaginal smears were evaluated daily and serum hormone levels were correlated with cycle and with ovarian morphology at necropsy. Exposure concentration-related effects of Hg degrees were evaluated by exposing rats to 0, 1, 2, or 4 mg/m3 Hg degrees vapor 2 h/day for 11 consecutive days. Tissue Hg levels correlated with exposure concentration and duration. Exposure of rats to 4 mg/m3 (but not 1 or 2 mg/m3) Hg vapor for 11 days resulted in significant decreases in body weights relative to controls. Estrous cycles were slightly prolonged in the 2 and 4 mg/m3 dose groups, and serum estradiol and progesterone levels were significantly different in the 4 mg/m3 group compared to controls. The alterations in cycle and hormones at the 4 mg/m3 exposure concentration were attributed to body weight loss and generalized toxicity. In the time-course study, rats were exposed to 2 mg/m3 Hg degrees or air beginning in metestrus and evaluated daily for 8 days. A lengthening of the cycle was detected and morphological changes were observed in the corpora lutea (CL) after exposure for 6 days. To determine if changes in the CL and cyclicity correlated with a functional defect, rats were exposed to Hg degrees vapor and evaluated for pregnancy outcome. There were no significant effects on pregnancy rate or numbers of implantation sites when rats were exposed to 1 or 2 mg/m3 Hg degrees for 8 days prior to breeding, or when exposed for 8 days after breeding. These studies indicate that exposure to Hg degrees vapor altered estrous cyclicity, but had no significant effect on ovulation, implantation, or maintenance of first pregnancy during exposure of short duration in female rats.     

非人灵长类模型在生殖发育毒性评价中的应用

随着生物技术药物研发的增加,使用非人灵长类动物进行发育和生殖毒性研究已越来越普遍。食蟹猴是发育和生殖毒性研究最理想的非人灵长类动物模型,这一种属在生殖和内分泌方面与人类十分类似。本文介绍了非人灵长类在发育毒性(胚胎-胎仔发育,围产期发育)和生殖毒性(雌性和雄性)研究中的应用,为灵长类发育和生殖毒性实验设计的优化提供参考。     

己烯雌酚对生殖系统的影响及机制的研究进展

环境雌激素是影响人类和动物健康的重要因素。己烯雌酚是酚类环境的一种雌激素,对雌性和雄性动物的生殖系统有影响。己烯雌酚可能通过雌激素受体、下丘脑-垂体-性腺轴、氧化机制和基因水平变化等对生殖系统产生影响,本文综述了己烯雌酚对生殖系统的影响及机制。     

The use of in vitro methods for assessing reproductive toxicity. Dichlorophenols

Environmental levels of dichlorophenols (DCPs) appear to be increasing. A paucity of knowledge exists concerning the impact of these agents on human health, including reproductive effects. Mice are being exposed to various DCPs to determine their toxic potential. In addition, the mouse in vitro fertilization method was used to evaluate the potential reproductive effects of a series of DCPs. This method is a preliminary reproductive screening procedure. In vitro penetration was depressed by 2,5-DCP, 3,4-DCP and 3,5-DCP. None of the agents affected sperm motility. Acridine orange fluorescent microscopy revealed that 3,4-DCP and 3,5-DCP disrupted the sperm acrosome; this could result in depressed penetration.