Two new isoflavones from the barks of Dalbergia hancei Benth.

Two new isoflavone compounds, Dalhancei A (1) and Dalhancei B (2), along with a known compound epicatechin (3) were isolated from 80% methanol extract of the barks of Dalbergia hancei Benth. The structures of compounds 1-3 were elucidated by comparison with the literature and physical data analysis, including optical rotation, MS, 1D and 2D NMR spectra. Compounds 1 and 2 showed weak inhibitory activity against tyrosinase at 16.22 mmol/L, with inhibition rates of 42.23 ± 0.18% and 45.68 ± 0.17%, respectively; compound 1 exhibited weak inhibitory activity against α-glucosidase with the inhibition rate of 43.72 ± 0.22% at 5.41 mmol/L, compounds 2 and 3 had better α-glucosidase inhibitory activity than compound 1 with IC50 values of 0.90 ± 0.18 and 0.41 ± 0.17 mmol/L, respectively.

Bisphenol A analogues in associations with serum hormone levels among reproductive-aged Chinese men.

BACKGROUND: Bisphenol A (BPA) as an endocrine disrupting chemical has been shown to alter reproductive endocrine function, but little is known on its analogues such as bisphenol F (BPF) and bisphenol S (BPS) with increasing usage and exposure. OBJECTIVE: To explore the associations between exposures to BPA, BPF and BPS and serum reproductive hormones among reproductive-aged Chinese men. METHODS: We measured BPA, BPF and BPS concentrations in repeated urine samples and multiple reproductive hormones in the serum samples collected from 462 men attending an infertility clinic in Wuhan, China. Linear regression models were applied to assess the associations between averaged urinary BPA, BPF and BPS levels and serum hormone concentrations, and restricted cubic spline (RCS) models were further utilized to explore potential non-linear associations. We also examined potential modifying effects by age and body mass index (BMI). RESULTS: There was little evidence of associations between BPA exposure and altered reproductive hormones. However, we found that elevated BPF and BPS exposures were in negative associations with estrogen (E2) levels and E2/T (total testosterone) ratio (all P for trends < 0.05), and that elevated BPS exposure was negatively associated with SHBG levels (P for trend = 0.09). Based on the RCS models, these linear negative associations except that between BPS exposure and E2/T ratio were further confirmed. In stratified analyses, BPF and BPS exposures in relation to reduced E2 and E2/T ratio were more pronounced among men aged > 30 years, whereas their associations with reduced SHBG levels were more pronounced among men aged ≤ 30. Also, BPS exposure in negative association with FSH only emerged among men with BMI ≥ 24 kg/m2 (P for interaction = 0.03). CONCLUSION: BPF and BPS exposures were negatively associated with male serum E2, E2/T ratio and SHBG levels, and these associations varied by age and BMI.

Organochlorine pesticide exposures, metabolic enzyme genetic polymorphisms and semen quality parameters among men attending an infertility clinic.

The associations of organochlorine pesticides (OCPs) with semen quality from human studies are conflicting, and also it is largely unknown whether the associations are modified by genetic polymorphisms. We aimed to evaluate the associations between serum concentrations of 18 OCPs and semen quality among 387 Chinese men, and further to examine the modifying effects by genetic polymorphisms in cytochrome P450 (CYP2E1) and glutathione S-transferase (GSTT1). Multivariable linear regressions were used to evaluate the relationships between serum OCP concentrations and semen quality, and the role of CYP2E1 and GSTT1 polymorphisms in modifying the associations were assessed. Multiple testing was adjusted using the false discovery rate (FDR). We observed that men with detectable concentrations of serum ɤ-HCH had a decrease in sperm motility of 7.07% (95% CI: -10.9%, -3.24%) compared to those with undetectable concentrations (FDR-P value = 0.02). Men with TT of CYP2E1 rs 915906 genotypes had higher median concentrations of serum dieldrin compared with those with CT/CC of CYP2E1 rs 915906 genotypes. There were interactions between CYP2E1 and GSTT1 polymorphisms and certain OCPs namely ɤ-HCH, δ-HCH, dieldrin, endosulfan I, and endrin aldehyde on semen quality. For example, elevated dieldrin levels in relation to decreased sperm concentration, sperm count, and sperm motility were only observed among men with CC of CYP2E1 rs2031920 genotypes (all Pinteraction < 0.05). However, these interactions were not statistically significant after the FDR adjustment. Our results suggested that CYP2E1 and GSTT1 polymorphisms may modify the effects of OCP exposures on semen quality. Due to the relatively small size samples, further investigation is warranted to confirm the findings.

Automatic phantom-less QCT system with high precision of BMD measurement for osteoporosis screening: Technique optimisation and clinical validation.

BACKGROUND: Currently dual-energy X-ray absorptiometry (DXA) and phantom-based quantitative computed tomography (PB-QCT) have been utilized to diagnose osteoporosis widely in clinical practice. While traditional phantom-less QCT (PL-QCT) is limited by the precision of manual calibration using body tissues, such as fat and muscle. OBJECTIVE: The aim of this study is to validate the accuracy and precision of one newly-developed automatic PL-QCT system to measure spinal bone mineral density (BMD) and diagnose osteoporosis. METHODS: A total of 36 patients were enrolled for comparison of BMD measurement between DXA and QCT. CT images of 63 patients were analyzed by both PB-QCT and newly developed automatic PL-QCT system, then the BMD results generated by the automatic PL-QCT were utilized to diagnose osteoporosis. The diagnostic outcomes were compared with that of DXA and PB-QCT to assess the performance of the new system. RESULTS: BMD test results showed that the automatic PL-QCT system had higher precision than previous studies performed with QCT, while maintaining similar capability to diagnose osteoporosis as DXA and PB-QCT. Area under curve (AUC) result of PL-QCT was larger than 0.8 for predicting spine DXA T-score in receiver operating characteristic (ROC) analysis. Pearson correlation analysis (r â€‹= â€‹0.99) showed strong linear correlation and Bland-Altman analysis (bias â€‹= â€‹3.0mg/cc) indicated little difference between the two methods. The precision result (CV â€‹= â€‹0.89%) represented good reproducibility of the new system. CONCLUSION: The traditional PL-QCT system has relatively low reproducibility due to the manual selection of the region of interest (ROI) of body tissues. Automatic selection of ROI in this new system makes the BMD testing more convenient and improves precision significantly. Compared with traditional BMD measurement methods, the automatic PL-QCT system had higher precision in accurate diagnosis of osteoporosis with great potential in translational research and wide clinical application. TRANSLATIONAL POTENTIAL STATEMENT: With high accuracy and precision, the automatic PL-QCT system could serve as an opportunistic screening tool for osteoporosis patients in the future. It could also facilitate related researches by providing more reliable data collection, both retrospectively and longitudinally.

Structural Characterization and Assessment of Anti-Inflammatory and Anti-Tyrosinase Activities of Polyphenols from Melastoma normale.

Polyphenols, widely distributed in the genus Melastoma plants, possess extensive cellular protective effects such as anti-inflammatory, anti-tyrosinase, and anti-obesity, which makes it a potential anti-inflammatory drug or enzyme inhibitor. Therefore, the aim of this study is to screen for the anti-inflammatory and enzyme inhibitory activities of compounds from title plant. Using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, the extract of Melastoma normale roots was separated. Four new ellagitannins, Whiskey tannin C (1), 1-O-(4-methoxygalloyl)-6-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-ß-d-glucose (2), 1-O-galloyl-6-O-(3-methoxygalloyl)-2,3-O-(S)-hexahydroxydiphenoyl-ß-d-glucose (3), and 1-O-galloyl-6-O-vanilloyl-2,3-O-(S)-hexahydroxydiphenoyl-ß-d-glucose (4), along with eight known polyphenols were firstly obtained from this plant. The structures of all isolates were elucidated by HRMS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW2 64.7 cells, we investigated the anti-inflammatory activities of compounds 1-4, unfortunately, none of them exhibit inhibit nitric oxide (NO) production, their IC50 values are all > 50 µM. Anti-tyrosinase activity assays was done by tyrosinase inhibition activity screening model. Compound 1 showed weak tyrosinase inhibitory activity with IC50 values of 426.02 ± 11.31 µM. Compounds 2-4 displayed moderate tyrosinase inhibitory activities with IC50 values in the range of 124.74 ± 3.12-241.41 ± 6.23 µM. The structure-activity relationships indicate that hydroxylation at C-3', C-4', and C-3 in the flavones were key to their anti-tyrosinase activities. The successful isolation and structure identification of ellagitannin provide materials for the screening of anti-inflammatory drugs and enzyme inhibitors, and also contribute to the development and utilization of M. normale.

Mangiferin exerts neuroprotective activity against lead-induced toxicity and oxidative stress via Nrf2 pathway.

Objective: The study was designed to assess the beneficial role of mangiferin (MGN) in lead (Pb)-induced neurological damages in the activation of Nrf2-governed enzymes, genes and proteins. Methods: A total of 96 weaned Wistar rats (48 males and 48 females, 26- to 27-day-old), weighing 50-80 g were used. The experiment was performed in six groups: normal group (control, n = 16), model group (chronic Pb exposed, n = 16), Dimercaptosuccinic acid (DMSA)-treated group (positive control, Pb + DMSA, n = 16), three MGN-treated groups with different doses (Pb + MGN, n = 48). Normal group freely had access to purified water. DMSA-treated group was given DMSA, which was clinically used as the standard treatment for moderate Pb poisoning, at 50 mg/kg (2 mL suspension with purified water) by intragastric gavage (ig) 4 continual days a week for 4 weeks, MGN-treated groups were given MGN at 50, 100, or 200 mg/kg (2 mL suspension with purified water) by ig daily for 4 weeks. At the end of the treatment, all rats were sacrificed and the brain samples were collected. The haematoxylin and eosin (H&E) staining was used for observation of histopathology. Commercial kit, real-time quantitative polymerase chain reaction (RT-qPCR), Western-blot and immunohistochemistry (IHC) detection were used to detect the mRNA and protein expression. Results: Eight weeks exposure to Pb-containing water resulted in pathological alterations, anti-oxidative system disorder in the brain, all of which were blocked by MGN in a Nrf2-dependent manner. Nrf2 downstream enzymes such as HO-1, NQO1, γ-GCS were activated. Nrf2, GCLC, GCLM, HO-1 mRNA and total Nrf2, Nuclear Nrf2, γ-GCS, HO-1 protein expression were affected too. Conclusion: MGN ameliorated morphological damage in the hippocampus. Its neuroprotective effects were achieved by the activation of the Nrf2 downstream genes. The data from this in vitro study indicates that MGN targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with Pb exposure. Thus, MGN could be an effective candidate agent for the Pb-induced oxidative stress and neurotoxicity in the human body.

[PI3K-Akt/LKB1-AMPK-mTOR-p70S6K/4EBP1 signaling pathways participate in the regulation of testis development and spermatogenesis: An update].

Male infertility is closely associated with spermatogenesis disorders triggered by aberrant gene expression or abnormal signaling pathways in the testis. The mammalian target of rapamycin (mTOR) is a central regulator of cell metabolism, playing an important role in regulating cell proliferation, differentiation, translation, actin polymerization, cycle progression, energy metabolism, autophagy, and other cellular activities. PI3K-Akt and LKB1-AMPK, the two well-defined classic signal transduction pathways, regulate the expressions of mTOR and its downstream p70S6K/4EBP1 through different molecular pathways. Recent studies show that mTOR-p70S6K/4EBP1 signaling participates in the regulation of the proliferation and differentiation of testicular cells and spermatogenesis. This review focuses on the role of PI3K-Akt/LKB1- AMPK-mTOR signaling cascades in testis development and spermatogenesis, providing some new perspectives for the studies of the molecular mechanism underlying male sterility.

Protective effects of mangiferin in subchronic developmental lead-exposed rats.

Lead is a ubiquitous environmental and industrial pollutant. Exposure to excessive amounts of lead is especially harmful to the central nervous systems of infants and young children, and oxidative stress has been reported as a major mechanism of lead-induced toxicity. To evaluate the ameliorative potential of antioxidant mangiferin (MGN) on lead-induced toxicity, Morris water maze test, determination of blood and bone lead concentration, determination of antioxidant status in plasma, as well as observation of ultrastructural changes in the hippocampus were carried out. In the present study, under a transmission electron microscope, ameliorated morphological damages in the hippocampus were observed in MGN-treated groups. Blood and bone lead concentration in MGN-treated groups lowered to some extent (p < 0.05, p < 0.01). The activities of antioxidant enzymes, glutathione (GSH) content, and the GSH/oxidized glutathione ratio in MGN-treated groups were increased, respectively. Further studies are needed to establish whether the observed differences were a direct cause of mangiferin on lead-induced toxicity or not. This study might provide clues for the treatment of lead-induced toxicity.

p,p'-DDE induces apoptosis and mRNA expression of apoptosis-associated genes in testes of pubertal rats.

One,1-dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. To elucidate the mechanism underpinning the testicular effects of p,p'-DDE, we sought to investigate apoptotic effects and mRNA expression of apoptosis-associated genes in the testis of pubertal rats, including Fas, FasL, calpain-1, cytochrome c, Bax, Bcl-w, Bak, and caspase-3, -8, -9, -12. Animals were administered with different doses of p,p'-DDE (0, 20, 60, 100 mg/kg body weight) every other day by intraperitoneal injection for 10 days. The results indicated that p,p'-DDE exposure at over 20 mg/kg body weight showed the induction of apoptotic cell death. p,p'-DDE could induce decrease in SOD and GSH-Px activity of serum in 60 mg/kg body weight group. Significant elevations in the mRNA levels of Fas, FasL, calpain-1, cytochrome c, Bax, Bak, and caspase-3, -8, -9, -12 were observed in testis of rat treated with p,p'-DDE. Taken together, these results lead us to speculate that in vivo exposure to p,p'-DDE might induce testicular apoptosis in pubertal rats through the involvement of Fas/FasL, mitochondria and endoplasmic reticulum-mediated pathways.

p,p'-DDE induces testicular apoptosis in prepubertal rats via the Fas/FasL pathway.

1,1-Dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. To elucidate the mechanism underpinning the testicular effects of p,p'-DDE, we sought to investigate Fas/FasL apoptotic pathway in the testis of prepubertal rats, including Fas, FasL, caspase-8, -3, and NF-kappaB. Animals were administered with different doses of p,p'-DDE (0, 20, 60, 100mg/kg b.wt) every other day by intraperitoneal injection for 10 days. The results indicated that p,p'-DDE exposure at over 20mg/kg b.wt showed the induction of apoptotic cell death. p,p'-DDE could induce increase in the MDA level, and decrease in SOD and GSH-Px activity. Significant elevations in the mRNA levels of Fas along with an increase in FasL, caspase-3, -8 were observed in 100mg/kg b.wt group. In protein level, p,p'-DDE could induce increase of FasL and reduction of procaspase-8. NF-kappaB p65 was activated by p,p'-DDE treatment in rat testis. In addition, the activities of caspase-3, -8 were increased in 100mg/kg b.wt group. Taken together, these results lead us to speculate that in vivo exposure to p,p'-DDE might induce testicular apoptosis in prepubertal rats through the Fas/FasL pathway.

[Action mechanism of p,p'-DDE and/or beta-BHC on JNK and MAPK signal transduction pathways in rat Sertoli cells].

OBJECTIVE: To study the action mechanism of p,p'-DDE and/or beta-BHC on JNK and MAPK signal transduction pathways in rat Sertoli cells in vitro. METHODS: We cultured the Sertoli cells isolated from rat testicular tissues for 2 days in vitro, divided them into a control group incubated with DMSO and 3 case groups exposed to p,p'-DDE and / or beta-BHC at the final concentration of 10, 30, 50 micromol/L for 24 hours, and then detected the expression levels of JNK and c-jun mRNA by two-step RT-PCR. RESULTS: Twenty-four hours after p,p'-DDE treatment, the grayscale values of JNK mRNA were 0.068 +/- 0.001, 0.164 +/- 0.002, 0.207 +/- 0.006 and 0.499 +/- 0.017, and those of c-jun mRNA were 0.122 +/- 0.002, 0.157 +/- 0.006, 0.218 +/- 0.007 and 0.289 +/- 0.004 respectively in the DMSO control and the 10, 30 and 50 micromol/L groups. The expressions of JNK and c-jun mRNA were elevated with increased concentration of p,p'-DDE, with significant differences between the control and the case groups (P < 0.05), and they were also significantly upregulated in the beta-BHC and p,p'-DDE + beta-BHC groups in a dose-dependent manner. The grayscale values of JNK mRNA in the p,p'-DDE, beta-BHC and p,p'-DDE + beta-BHC groups at the concentration of 10 micromol/L were 0.164 +/- 0.002, 0.149 +/- 0.003 and 0.178 +/- 0.004, and those of c-jun mRNA were 0.157 +/- 0.006, 0.131 +/- 0.004 and 0.172 +/- 0.002, respectively, both significantly higher in the combination group than in the former two (P < 0.05). And the same was the case with the 30 and 50 micromol/L concentrations. CONCLUSION: Both p,p'-DDE and beta-BHC can enhance the expressions of JNK and c-jun in Sertoli cells, and their combination can produce even more obvious effect.

[Effects of p,p'-DDE and beta-BHC on the apoptosis of Sertoli cells in vitro].

OBJECTIVE: To explore the effects of p,p'-DDE and beta-BHC on the apoptosis of Sertoli cells in vitro via activation of Caspase. METHODS: Sertoli cells were treated in vitro for 24 hours with a serial concentrations of p,p'-DDE (10, 30 and 50 micromol/L), beta-BHC (10, 30 and 50 micromol/L) and p,p'-DDE + beta-BHC (10, 30 and 50 micromol/L). The inhibitory group was first treated with 100 micromol/L Caspase-3 inhibitor Ac-DEVD-CHO treating for 2 hours before 50 micromol/L p, p'-DDE + 50 micromol/L beta-BHC 24 hours-treatment. The vitality of Sertoli cells was determined by MTT and the apoptosis rate was measured by AO/EB double fluorescence staining. The expressions of Caspase-3, Caspase-8 and Caspase-9 were determined by RT-PCR. RESULTS: Average optical density (A) values were 0.498 +/- 0.039, 0.481 +/- 0.065, 0.397 +/- 0.032 and 0.286 +/- 0.049 in p,p'-DDE groups (10, 30, 50 and 70 micromol/L), and 0.518 +/- 0.103, 0.490 +/- 0.060, 0.454 +/- 0.054 and 0.302 +/- 0.030 in beta-BHC groups (10, 30, 50 and 70 micromol/L). In the mixture-treated groups (10, 30 and 50 micromol/L), the average A values were 0.483 +/- 0.048, 0.473 +/- 0.058 and 0.337 +/- 0.052. Compared with the solvent control group (0.527 +/- 0.022) , 50 micromol/L group of p, p'-DDE, beta-BHC or their mixture caused a significant decrease of Sertoli cell viability (t values were 4.599, 2.716, 6.537 respectively, P < 0.05). AO/EB double fluorescence staining analysis showed that apoptosis rates of Sertoli cells were significantly increased with all treated groups. The expressions of Caspase-3, Caspase-8 and Caspase-9 were upregulated as the concentrations of p,p'-DDE, beta-BHC and their mixture were increased. CONCLUSION: p,p'-DDE, beta-BHC and their mixture could induce the apoptosis of Sertoli cells in vitro which was associated with activation of Caspase-3 mediated by cleavage of Caspase-8 and Caspase-9.

[Investigation on one-pot extraction of active ingredient group from Yupingfeng powder by HPLC].

The extraction of active ingredient group, i.e., prim-o-glucosylcimifugin, astragaloside, and 5-o-methylvisammiosode from Yupingfeng powder with one-pot method was studied in this work. A HPLC method was used to determine the content of each active constituent mentioned above in the extract. The influences of extraction temperature, time, volume percent of ethanol in water and its amount added on the content and yield of active ingredient group were investigated by orthogonal test. The experimental results showed that the optimized extraction conditions were as follows: 1g of Yupingfeng powder was one-pot extracted for 4 hours at 80 degrees C with 90% ethanol as solvent, and the yield and content of active ingredient group were 0.16%, 0.53% respectively. The active ingredient group in Yupingfeng powder could be effectively one-pot extracted under the conditions above.

Inhibitory effects of selenium on telomerase activity and hTERT expression in cadmium-transformed 16HBE cells.

OBJECTIVE: To investigate the effects of sodium selenite on telomerase activity and expression of hTERT mRNA in cadmium-transformed 16HBE cells. METHODS: Telomerase activity and expression of genes were measured after cultured cadmium-transformed 16HBE cells were exposed to sodium selenite at different doses (0.625, 1.25, 2.50, 5.00 micromol/L) for 24 hours. RESULTS: Selenium decreased telomerase activity in cadmium-transformed 16HBE cells. There existed an obvious dose-effect relationship between the selenium concentration and these changes. The expression of hTERT and c-myc mRNA also decreased but the expression of mad1 mRNA increased after exposure to selenium for 24 hours. No difference was found in expression of hTRF1 and hTRF2 mRNA after incubated with sodium selenite for 24 hours, compared with control group. CONCLUSION: Selenium inhibits telomerase activity by decreasing hTERT and c-myc mRNA expression and increasing mad1 mRNA expression in cadmium-transformed 16HBE cells and selenium concentration is significantly correlated with these changes.

[Effect of p, p'-DDE on DNA damage and expression of FasL gene of rat Sertoli cell in vitro].

OBJECTIVE: To study the effects of p, p'-DDE on DNA damage and expression of FasL gene of rat Sertoli cell in vitro. METHODS: After separating Sertoli cells from testicular tissue of rats, we cultured these cells for 3 days and then added different doses of p, p'-DDE into the culture medium to study its effect on DNA damage and FasL gene expression with the method of SCGE and RT-PCR. RESULTS: DNA migration and FasL gene expression of Sertoli cell significantly increased with the increase of the dose of p, p'-DDE. CONCLUSION: p, p'-DDE could induce DNA damage and FasL gene expression of Sertoli cells of rat testis. p, p'-DDE might induce the Sertoli cell damage and destroy the dynamic process of spermatogenesis through the Fas/FasL pathway, which might lead to oligozoospermatism.

[Study on reproductive and developmental toxicity of the pregnant mice and their foetus co-administered by p, p'-DDE and beta-BHC].

OBJECTIVE: To explore effects of p, p'-DDE and beta-BHC on reproduction and development in mice. METHODS: The pregnant Kunming SPF mice of 12 to 14 days were co-administered by oral gavage for 3 days at different concentrations of 0, 1, 5 and 10 mg/kg bw of p, p'-DDE and beta-BHC. The concentrations of estradiol (E2) and progesterone (P) in sera of the dosed mice were determined by the Serozyme kits (Bio-Ekon biotechnology Co., Beijing, China), following the procedures described by the manufacturer. RT-PCR was employed to detect abundant expression of alpha-estrogen receptor (alpha-ER) gonadtropin releasing hormone (GnRH) and beta-endorphin (beta-EP) mRNA in placentae. RESULTS: (1) Reproductive effects: with increase of the administered p,p'-DDE and P-BHC,the organ coefficient of uterus and its intraluminal fluid increased, the unterine nidation quantity decreased, the anogenital distance (AGD) and ratio of female to male raised, the concentration of estradiol and progesterone in sera of the dosed mice went up, and the abundant expression of alpha-ER and GnRH mRNA rised while beta-EP dropped in placentae in a dose-dependant manner. Significant difference of these indexes were found between the treat groups and control (P < 0.05). (2) Developmental effects: with increase of the administered p,p'-DDE and beta-BHC, the gained weights of pregnant mice reduced, organ coefficient of liver increased,the quantity of live foetus decreased, the times of adverse pregnancy outcome went up, and the percent of female foetus increased. They all presented a dose-effect relation and significance of difference (P < 0.05). CONCLUSION: p, p'-DDE and beta-BHC disrupt reproductive function, thereby result in dysreproduction and maldevelopment, and unbalance of ratio of female to male.

[Effects of selenium on expression of TERT, c-Myc and p53 induced by cadmium in rat liver].

OBJECTIVE: To study the effects of sodium selenite on expression of telomerase reverse transcriptase mRNA, c-Myc and p53 induced by cadmium chloride in rat liver. METHODS: Male SD rats were divided randomly into 6 groups, each group had 5 animals. The groups comprised the control group, Se group (5 micromol/kg sodium selenite), 5 micromol/kg cadmium chloride group, 10 micromol/kg cadmium chloride group, Se (5 micromol/kg sodium selenite) + 5 micromol/kg cadmium chloride group, Se (5 micromol/kg sodium selenite) + 10 micromol/kg cadmium chloride group. After 48 hours of the first injection, the expression of TERT mRNA was measured with RT-PCR and c-Myc, and p53 proteins were measured by immunohistochemistry method. RESULTS: Compared with control group, the expression of TERT was increased in 5 micromol/kg Cd group and 10 micromol/kg Cd group, c-Myc protein was increased in 10 micromol/kg Cd group, and the expression of p53 protein was increased in 5 micromol/kg group and 10 micromol/kg Cd group. TERT expression in Se + 10 micromol/kg Cd group was lower than that of 10 micromol/kg Cd group significantly. c-Myc protein was decreased in Se + 10 micromol/kg Cd group compared with 10 micromol/kg Cd group. p53 protein of Se + 5 micromol/kg Cd group and Se + 10 micromol/kg Cd group were decreased significantly compared with 5 micromol/kg Cd group and 10 micromol/kg Cd group respectively. CONCLUSION: The cadmium at the doses of between 5 and 10 micromol/kg can activate TERT and up-regulate c-Myc and p53 proteins. The selenium at the dose of 5 micromol/kg has the antagonistic effect on expression of TERT, c-Myc and p53 induced by cadmium in rat liver.

[Effects of p,p'-dDE on the expression of androgen-binding protein, transferrin and inhibin B mRNA in rat sertoli cells].

OBJECTIVE: To explore effects of p, p'DDE on the expression of androgen binding protein (ABP), transferrin (Tf) and inhibin B (INH B) mRNA in testis Sertoli cells of Sprague Dawley rats. METHODS: A method has been set up to obtain a large number of viable Sertoli cells from SD rats of 18-20 days of age. With a series of concentration p,p'-DDE (10, 30, and 50 micromol/L) co-incubating the Sertoli cells in vitro, the expression of ABP, Tf and INH B mRNA were determined by RT-PCR. RESULTS: a) With increase of the incubated p, p'-DDE, the expression of ABP mRNA in Sertoli cells went up while that of Tf and INH B dropped in a dose-dependent manner (P < 0. 05). b) The correlation analysis among ABP, Tf and INH B showed that negative relationships were found between ABP and Tf or INH B, respectively (r = - 0. 391 3, P = 0. 032 5; r = - 0.235 2, P = 0.0158), and that positive correlation was indicated between Tf and INH B (r =0.4516, P =0.0047). CONCLUSION: p,p'-DDE is a reproductive toxicant which disrupts the transcription of ABP, Tf and INH B in rat Sertoli cells so as to result in reproductive dysfunction.

[Effects of residues of organochlorine pesticides on reproductive endocrine in human].

OBJECTIVE: To explore effects of residues of organochlorine pesticides on reproductive endocrine in human. METHODS: The accumulative levels of the pesticides in the pregnant women's venous blood were determined and were grouped to understand the associations among the pesticides, hormones, and genes. RESULTS: (1) With the increase of blood burden of organochlorine pesticides, levels of the hormones such as follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P) in the maternal blood and FSH, luteinizing hormone (LH) and E2 in the umbilical cord blood increased in dose-effect manner, respectively. However, the hormones, for example, LH in the women blood and P in the cords blood decreased respectively with the rising pesticides' levels and an obvious dose-effect relationship was found. (2) The expressional abundances of alpha-estrogen receptor (alpha-ER), beta-endorphin (beta-EP) and gonadotropin releasing hormone (GnRH) in the placentae and alpha-ER and beta-EP in the cord tissues went up respectively in dose-effect manner following the rising pesticides' burdens. (3) The times of the previous adverse pregnancy outcomes increased with the increase of the residues' burdens and there were significant differences between the control and various residue groups, but the times in the high-residue was smaller than that in the mid-residue group (P < 0.01). The average weights of the newborn in various residue groups were heavier comparing to the control. There was no significant difference between the high residue group and the control. However, significances existed among the low, intermediate, and control group (P < 0.05). Moreover, the rank from high to low was the low-residue, mid-residue and high residue group. CONCLUSION: The residues of organochlorine pesticides (DDT and BHC and their metabolites) possess reproductive and developmental toxicities, and present mostly the estrogenic activity under the joint exposure in which the total BHC concentration was higher than that of the total DDT in maternal blood.

Effects of fluoride on lipid peroxidation, DNA damage and apoptosis in human embryo hepatocytes.

OBJECTIVE: To investigate the effects of fluoride on lipid peroxidation, DNA damage and apoptosis in human embryo hepatocyte L-02 cells. METHODS: Lipid peroxide (LPO) level, reduced glutathione (GSH) content, DNA damage, apoptosis, and cell cycle analysis were measured after in vitro cultured L-02 cells were exposed to sodium fluoride at different doses (40 microg/mL, 80 microg/mL, and 160 microg/mL) for 24 hours. RESULTS: Fluoride caused an increase of LPO levels and a decrease of GSH content in L-02 cells. There appeared to be an obvious dose-effect relationship between the fluoride concentration and the observed changes. Fluoride also caused DNA damage and apoptosis and increased the cell number in S phase of cell cycle in the cells tested. There was a statistically significant difference in DNA damage and apoptosis when comparing the high dose of fluoride treated cells with the low dose of fluoride treated cells. CONCLUSION: Fluoride can cause lipid peroxidation, DNA damage, and apoptosis in the L-02 cell experimental model and there is a significant positive correlation between fluoride concentration and these pathological changes.