Doses Of Nonylphenol Research Articles

The effect of different doses of nonylphenol on the blood-testicular barrier integrity, hormone level, and DNA damage in the testes of rats.

Determining the molecular characteristics of the damage caused by NP exposure in the testis is very important for understanding the source of the damage and developing treatment methods accordingly. Therefore, in this study, it is aimed to evaluate the toxic effects that different doses of NP may cause in the testis, including blood-testicular barrier integrity and sperm DNA damage. For this purpose, 50 adult male Wistar albino rats were used in the study. Low, medium, and high-dose NP groups and the corn oil group were formed. After NP administration at determined doses for 15 days, the testis tissue taken under anesthesia was fixed in formaldehyde. Paraffin blocks were embedded using the routine histological tissue follow-up method. Histopathological and immunohistochemical analyses were performed by taking 5μm thick sections from paraffin blocks. The other testicular tissue was taken for the Western blot, Elisa, and comet methods, and the findings of sperm DNA analysis and the blood-testicular barrier were examined. NP caused the seminiferous epithelium to be disorganized and have significantly fewer cells in the testes of rats in different dose NP-induced groups. Compared with the control group, mTOR, Cx43, SCF, and HSP70 protein levels were decreased, while the expression of MMP-9 levels was increased in the different NP dose groups. Furthermore, tissue testosterone and inhibin B levels and SF-1 immunoreactivity intensity gradually decreased depending on the dose increase of NP. DNA damage of testicular tissues were increased in NP groups depending on NP dose. These results suggest that it is evident that NP, a commonly used industrial chemical, is an endocrine disrupting chemical (EDC) with estrogenic activity exerting adverse effects on health and that urgent measures are needed regarding the use.

Evaluation of the genotoxic effect of nonylphenol applied in different doses on the bone marrow

Nonylphenols are endocrine disrupting toxic compounds and are widely used. For this reason, our study aimed to investigate the genotoxic effect of nonylphenols applied at different doses on mouse bone marrow cells. Groups were classified as control group, the sham administered only group, low dose, medium dose and high dose nonylphenol administered group. After euthanasia, polychromatic erythrocyte/Normochromatic erythrocyte ratio and micronuclear polychromatic erythrocyte count were determined in femur bone marrow cells and analyzed to detect DNA damage. While polychromatic erythrocyte/Normochromatic erythrocyte ratio was found to be lower in the groups treated with different doses of nonylphenol, especially in the group treated with high-dose nonylphenol, this decrease was not statistically significant. When the micronucleated polychromatic erythrocyte values were examined, it was observed that there was a statistically significant increase, especially in the medium and high dose groups compared to the control. High-dose nonylphenol has a toxic effect and may have a long-term genotoxic effect such as cancer development by interacting with genotoxic agents.

Disturbance in Some Fertility Biomarkers Induced and Changes in Testis Architecture by Chronic Exposure to Various Dosages of Each of Nonylphenol or Bisphenol A and Their Mix.

Simple SummaryIn this study, 70 male albino rats were allocated to the control group (GI) and were given 1 mL of ethanol; G, II, and G III were treated with 100 mg/Kg of each of BPA and NP, G IV and G V were treated with 25 mg/Kg of each of BPA and NP, G VI was given a mixture of a high dose of BPA and NP, and G VII was given a mixture of a low dose of BPA and NP. A significant elevation in the TNF Alpha, TNF Beta, and Caspase 3 serum was recorded individually and in the groups treated with high doses. In conclusion, exposure to BPA and NP strongly impacts antioxidants, immune-inflammatory mediators, and testicular tissue architecture. Furthermore, the data from this investigation support the idea that exposure to BPA and NP in daily life has multiple damages.This investigation was conducted to demonstrate the potential impacts of different doses of Bisphenol A (BPA) or Nonylphenol (NP) and their mixtures on some biological activities in male albino rats. Seventy male albino rats were allocated to the control group (GI) and were given 1 mL of ethanol. G II and G III were given 100 mg/kg of each of BPA and NP, G IV and G V were given 25 mg/kg of each of BPA and NP, G VI was given a high dose of BPA and NP, and G VII was given a low dose of BPA and NP. All animals were treated orally for 60 days. Serum biomarkers of oxidative stress, antioxidants, immune-inflammatory mediators, and apoptotic markers were determined, as well as a histopathological examination of the testis at the end of the experimental period. The results obtained showed a pronounced increase in malondialdehyde (MDA), protein carbonyl (PC), and 4-hydroxynonenol (4-HNE), concomitant with a significant reduction in serum Superoxide dismutase (SOD), catalase enzyme (CAT), and total antioxidant capacity (TAC) in all treated groups. A significant elevation in TNF Alpha, TNF Beta, and Caspase 3 serum was recorded individually and in the groups treated with high doses. The disturbance is represented by histological damage in the testis in the germinal epithelium and a decrease in spermatozoa inside the lumen of seminiferous tubules. The effects on testis tissues were dose-dependent, pronounced in mixture doses, and remarkable in higher doses. In conclusion, exposure to BPA and NP strongly impacts antioxidants, immune-inflammatory mediators, and testis tissue architecture. Furthermore, the data from this investigation support the idea that exposure to BPA and NP in daily life has multiple damages.

The effect of nonylphenol exposure on the stimulation of melanomacrophage centers, estrogen and testosterone level, and ERα gene expression in goldfish

The present study tried to measure the formation of melanomacrophage centers (MMCs) in various organs of male and female goldfish exposed to nonylphenol (NP) and aimed to assess its relationship with the main sexual hormones, estrogen receptor expression, and the pigment content of the MMCs. Immature goldfish were exposed to 10−6 and 10−7 M NP for 25 days. After obtaining blood for measuring testosterone and estrogen (E2) levels, tissue samples were collected from various organs for histological studies, quantifying pigments using ImageJ software and chemical analysis, and measuring ERα gene expression. Results showed that the order of forming MMCs in various organs exposed to NP was liver > spleen > kidney, and the order of ERα gene expression was liver > testes > spleen > kidney in the male, and liver > spleen > kidney > ovaries in the female. Among the three pigments present in MMCs after exposure to the two doses of NP, melanin was more obvious (especially in the liver) and increased mostly in a dose-dependent manner in both sexes (especially in the male). Chemical analyses confirmed these results. Measurement of testosterone and E2 level in male and female goldfish showed that NP had more effect on the concentration of these hormones in male fish, indicating more endocrine-disrupting potential of NP against the male fish. Generally, the increase of melanin content of melanomacrophage centers coincided with the increase of ERα gene expression and decrease of testosterone level in goldfish after exposure to NP.

Dose- and time-effects responses of Nonylphenol on oxidative stress in rat through the Keap1-Nrf2 signaling pathway

Nonylphenol (NP) is a representative environmental endocrine-disrupting compound that can induce oxidative stress in organisms. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway acts an important role in preventing oxidative stress. The aim of this study was to investigate the influence of oxidative stress caused by NP on Keap1-Nrf2 pathway in rats. Rats were treated with NP (30, 90, 270 mg/kg) for different exposure time (7, 14 and 28 days). The levels of reactive oxygen species (ROS) in serum and glutathione S-transferase (GST), UDP-Glucuronosyl Transferase (UGT) in liver were detected by ELISA kits. Western blot was used to detect Keap1, Nrf2 protein expression in liver and cerebral cortex. The results showed that 28 days of NP exposure significantly increased ROS levels in NPH group. And 14 days exposure to NP significantly enhanced the levels of GST and UGT, while 28 days of exposure showed a suppressive effect. In liver, Keap1 levels was upregulated at 7, 14 and 28 days of NP exposure, while nuclear Nrf2 levels decreased at 7 and 28 days but increased at 14 days. In cerebral cortex, Keap1 and Nrf2 expression increased at 14 days but decreased at 28 days. Besides, with the prolongation of NP exposure time, the GST and UGT levels in NPM and NPH groups were increased firstly and then decreased, while Keap1 and Nrf2 protein levels were constantly decreased in liver and cerebral cortex. In conclusion, the lower dose and shorter exposure time of NP activated the Keap1-Nrf2 pathway that may reduce the damage of oxidative stress, but when further exposed to NP at higher dose and time, the pathway could be inhibited.

Toxic Effects of Nonylphenol on Neonatal Testicular Development in Mouse Organ Culture.

Nonylphenol (NP) is an alkylphenol that is widely used in chemical manufacturing. Exposure to this toxic environmental contaminant has been shown to negatively affect the reproductive system. Herein, we evaluated the toxicity of NP in mouse testes, while using in vitro organ culture. Mouse testicular fragments (MTFs), derived from five-day postpartum neonatal mouse testes, were exposed to different concentrations of NP (1–50 μM) for 30 days. The results showed that NP impaired germ cell development and maintenance. Furthermore, NP significantly downregulated the transcript levels of both undifferentiated and differentiated germ cell marker genes relative to those in controls. In particular, a high dose of NP (50 µM) led to complete germ cell depletion and resulted in spermatogenic failure, despite the presence of Sertoli and Leydig cells. In addition, the mRNA expression of steroidogenic enzymes, such as steroidogenic acute regulatory protein (STAR), Cytochrome P450 Family 11 Subfamily A Member 1 (Cyp11α1), Cytochrome P450 17A1 (Cyp17α1), and androgen receptor (AR), increased with increasing concentration of NP. Conversely, the expression of estrogen receptor alpha (ESR1) and Cytochrome P450 family 19 subfamily A member 1 (Cyp19α1) in NP-exposed MTFs decreased when compared to that of the control. Taken together, this study demonstrates that NP has a negative effect on prepubertal spermatogenesis and germ cell maintenance and it disrupts steroidogenesis and induces hormonal imbalance in MTFs.

Toxic effects of perinatal maternal exposure to nonylphenol on lung inflammation in male offspring rats

The incidence of asthma and its related allergic diseases has increased dramatically over the last decade. Asthma is a complex disease caused by genetic and environmental factors. Nonylphenol (NP), a typical endocrine disrupting chemical (EDC), is a major current focus in asthma research. Pregnant Sprague-Dawley rats (n = 8–10 per group) were given a consecutive daily dose of NP (25, 50, or 100 mg/kg/day) or an equivalent volume of vehicle by gavage from gestational day 7 until postnatal day (PND) 21. Exposure to 100 mg/kg NP increased the body mass of the offspring on PND 43. Perinatal exposure to NP in maternal rats led to a dose-dependent increase of NP level in the lung tissue of the offspring. The numbers of lymphocytes and neutrophils in bronchoalveolar lavage fluid were significantly higher in the 100 mg/kg NP group than those in the control. Histopathological examination of the lung showed that exposure to high dose NP resulted in a slightly thickened bronchiolar smooth muscles with inflammatory cell infiltration. In the cytoplasm of type II epithelial cells, osmiophilic lamellar bodies were observed, with emptied lamellar bodies. NP significantly increased the expressions of high mobility group box 1 protein (HMGB1) mRNA and nuclear factor κB (NF-κB) mRNA in the lung tissue of the offspring in a dose dependent manner. Similarly, the expressions of HMGB1, NF-κBp65 and estrogen receptor-β (ER-β) proteins increased with an increase of NP dose. NP content was positively correlated with the expressions of HMGB1 and NF-κB mRNA as well as HMGB1, NF-κBp65, and ER-β proteins in the lung tissue of offspring. Perinatal exposure to NP from the maternal rats might induce airway inflammation in the offspring, which may be due to NP-induced infiltration of inflammatory cells into the airway, and pathological alterations in airway structure as well as abnormal expression patterns of inflammation-related genes, proteins (including HMGB1 and NF-κB) and estrogen receptor β.

Depressive behavior induced by nonylphenol and its effect on the expression of ER-α and ER-β in nerve cells of rats

Objective: To investigate the effects of nonylphenol (NP) exposure on the depressive behavior in rats, and the effects of the expressions of estrogen receptor-α (ER-α) and estrogen receptor-β (ER-β) in nerve cells in vivo and vitro. Methods: Forty male SD rats were randomly divided into 4 groups: blank control group (0 mg/kg), low dose group (0.4 mg/kg), middle dose group (4 mg/kg) and high dose group (40 mg/kg), which were exposed to NP for 180 days. The exposure dose of NP in HT22 was 20μM, which was divided into4 groups: blank control group, NP group, ICI182780 group and ICI182780+NP group. Results: In vivo, in the open field experiment, the number of entries in the central area and duration of attention in central square decreased gradually in the NP high dose group compared with the control (F = 3.561, p = .029). In forced swimming experiment, with the increase of NP dose, the immobility time increased, and the increasing degree of middle dose group and high dose group was higher than that of the low dose group (F = 3.047, p = .048). The concentrations of serum dopamine (DA) in the middle dose and high dose groups decreased greatly compared with the control (F = 3.967, p = .023). NP exposure at the doses of 4 mg/kg and 40 mg/kg induced an increase in the level of serum corticosterone compared to the control (F = 11.536, p<.001). Compared with the control group, the expression of ER-β decreased gradually with an increase of NP dose in the NP treatment groups (F = 4.513, p = .014). In vitro, the activity of HT22 cells decreased with an increase of NP dose (F = 316.6, p<.001). When the dose of NP was 200 μM, the growth inhibition rate of HT22 cells was (0.54±0.11)%. The expression levels of ER-α and ER-β in ICI182780+NP group was lower than those in the control and ICI182780 groups, but higher than those in the NP group (F = 1.592, p=.266; F = 10.166, p=.004). Conclusion: Long-term exposure to NP could induce the alterations in depressive behavior, and the levels of neurotransmitters as well as the expression of ER in the hippocampus of rats. Moreover, NP could reduce the activity of HT22 cells and decrease the expression levels of ER-α and ER-β in vitro.

Effects of separate or combined exposure of nonylphenol and octylphenol on central 5-HT system and related learning and memory in the rats

This study evaluated toxic effects of nonylphenol (NP) and octylphenol (OP) on central 5-hydroxytryptamine (5-HT) system and related learning and memory in the rats. Male Sprague-Dawley rats were exposed to NP (30, 90, or 270 mg/kg), OP (40, 120, or 360 mg/kg), or a mixture of NP and OP [(mixed with the corresponding NP, OP alone exposed low, medium and high dose according to the natural environment exists NP:OP = 4:1; NOL (24 mg/kg NP+8 mg/kg OP), NOM (72 mg/kg NP+24 mg/kg OP), NOH (216 mg/kg NP+72 mg/kg OP)] by gavage every other day for 30 d. Learning and memory were assessed using a passive-avoidance test. Levels of estrogen receptor β (ERβ), 5-HT, tryptophan hydroxylase 2 (TPH2), monoamine oxidase (MAOA) enzyme, serotonin transporter (SERT), the vesicular monoamine transporter 2 (VMAT2), 5-hydroxytryptamine 1 A (5-HT1A), 5-hydroxytryptamine 3 A (5-HT3A), 5-hydroxytryptamine 3B (5-HT3B), 5-hydroxytryptamine 4 A (5-HT4A) and 5-hydroxytryptamine 6 A (5-HT6A) were measured using ELISA kits. Levels of ERβ, MAOA, SERT, VMAT2, 5-HT1A, 5-HT3A, 5-HT3B, 5-HT4A and 5-HT6A in rat hippocampal reduced by a high dose of NP and/or OP. Levels of TPH2 in rat midbrain and 5-HT in rat hippocampal increased by a high dose of NP and/or OP. In addition, latency was significantly shorter and errors were significantly greater in the high dose NP and NP+OP (NO) groups. Taken together, these results suggest that NP and/or OP may affect learning and memory in rats by inhibiting levels of ERβ, which could then lead to decreases in levels of 5-HT1A, 5-HT3A, 5-HT3B, 5-HT4A, and 5-HT6A in the rat hippocampus. These findings suggested that separate and combined exposure to NP and OP could produce toxic effects on central 5-HT system and related learning and memory in the rats.

Interruption of immune responses in primary macrophages exposed to nonylphenol provides insights into the role of ER and NF-KB in immunotoxicity of Persian sturgeon

The severe decline in population of sturgeons due to pollution highlighted poor understanding about the immunotoxicological responses of sturgeons. This study was designed in three experiments to find out how nonylphenol (NP) interrupts some pro-inflammatory immune parameters in macrophages from Persian sturgeon (Acipencer persicous) as the oldest vertebrate model conserving intact innate immune system. After determination of IC50 values of NP (200 μM), some pro-inflammatory immune parameters and induced apoptosis in macrophages at low dose (10 nM) and high dose (100 nM) of NP and of 17β estradiol (E2) (positive control) were determined after 6, 24 and 48 h of the exposure (as the first experiment). The two doses of NP induced pro-inflammatory reaction and apoptosis with strong correlations, whereas this result was observed more obviously in high dose of E2. In the second experiments, the macrophages were exposed to the two doses of NP along with estrogen receptor alpha (ERα) antagonist, which consequently decreased the induction of pro-inflammatory reactions. Similarly, in the third experiment, NF-KB and ERα antagonists were used and pro-inflammatory reactions decreased compared to the control group (P < 0.05). Decreasing correlation between immune parameters following the second and third experiments verified interaction between ERα and NF-KB pathways. Thus, NP could be immune disrupter and apoptosis inducer in sturgeon macrophages in vitro, even in low dose. For the first time, this study revealed that NP can induce pro-inflammatory reactions in macrophages derived from sturgeons.

Antioxidant responses and DNA damage in primary hepatocytes of Van fish (Alburnus tarichi, Güldenstadt 1814) exposed to nonylphenol or octylphenol

Alkylphenols, a nonionic surface-active agent group, such as nonylphenol (NP) and octylphenol (OP) are important endocrine-disrupting chemicals (EDC). In this study, the dose- and time-dependent effects of NP and OP were investigated in the primary hepatocyte culture of Van Fish. In this study, samples were taken at different times and biochemical parameters were studied separately. The effects of the chemicals used on SOD, CAT, GSH-Px, MDA, and 8-OHdG were investigated in hepatocyte culture. The antioxidants SOD and CAT were observed to increase in all groups in the primary hepatocyte cultures at the 24th hour after NP and OP administration, whereas the GSH-Px level was observed to increase with OP at the 24th hour and with NP at the 48th hour. The MDA level was observed to reach its highest value for both chemicals in the 24th hour, and the 8-OHdG level was observed to increase toward the end of the follow-up time, compared to the control group (p < 0.05). In conclusion, different doses of NP and OP were found to induce an increase in the levels of antioxidants and the MDA level in Van Fish primary hepatocyte culture. DNA damage, on the other hand, may be considered to appear after longer-term exposure to NP and OP.

Ecotoxicological effects of bisphenol A and nonylphenol on the freshwater cladocerans Ceriodaphnia silvestrii and Daphnia similis

Toxicities of bisphenol A (BPA) and nonylphenol (NP) to the neotropical freshwater cladocerans Ceriodaphnia silvestrii and Daphnia similis were studied under laboratory conditions. Acute exposures to BPA generated mean 48-h EC50 values of 14.44 (6.02–22.85) mg L−1 for C. silvestrii and 12.05 (1.73–22.37) mg L−1 for D. similis. When the organisms were exposed to acute doses of NP, mean 48-h EC50 values were 0.055 (0.047–0.064) mg L−1 (C. silvestrii) and 0.133 (0.067–0.200) mg L−1 (D. similis). Ceriodaphnia silvestrii was also tested in chronic bioassays, which resulted in mean 8-d IC25 values of 2.43 (2.16–2.69) mg L−1 BPA [no observed effect concentration (NOEC): 1.38 mg L−1] and 0.020 (0.015–0.026) mg L−1 NP (NOEC: 0.015 mg L−1). These laboratory tests are valuable to broaden the understanding of the environmental threat posed by BPA and NP in aquatic ecosystems, and to increase the knowledge about the sensitivity of neotropical indigenous species to these contaminants. In addition to the laboratory bioassays, species sensitivity distributions were used to suggest protective concentrations of BPA and NP to prevent adverse effects on freshwater organisms. According to the obtained results, concentrations lower than 36.47 µg L−1 BPA and 1.39 µg L−1 NP are not expected to adversely impact aquatic organisms in natural ecosystems.

Influence of nonylphenol and octylphenol exposure on 5-HT, 5-HT transporter, and 5-HT2A receptor.

Nonylphenol (NP) and octylphenol (OP) are priority environmental contaminants that have a potential role as endocrine disruptors. They can be biomagnified in the food chain and pose an estrogenic health risk to human health. A 28-day oral toxicity study was performed to observe the impact of single and combined exposure to NP and OP on 5-HT transporter (SERT) as well as 5-HT2A receptor. Results showed that the 5-HT levels in rat plasma increased with exposure to middle-dose and high-dose NP, to high-dose OP, and to low, middle, and high doses of combined NP and OP (P<0.05), while the 5-HT levels in rat platelets increased when exposed to NP/OP or combined NP and OP of middle or high dose (P<0.05). The expression levels of SERT in rat platelets decreased when exposed to high-dose NP/OP or high dose of combined NP and OP (P<0.05). Meanwhile, the expression levels of 5-HT2A in rat platelets decreased when exposed to high-dose NP/OP as well as combined NP and OP (P<0.05). These findings suggested that exposure to NP and OP could influence the metabolic network of 5-hydroxytryptamine via transportation and receptor binding pathways.

Detection of Bisphenol A and Nonylphenol in Rat's Blood Serum, Tissue and Impact on Reproductive System.

IntroductionBisphenol A (BPA) and Nonylphenol (NP) have estrogen-like activity, and some of their adverse biological effects have been demonstrated. This study was designed to determine the association of plasma and tissue concentrations of BPA and NP and changes in the parameters of the reproductive system in rats.MethodsMale Wistar rats were administered three doses of BPA and NP (5, 25, and 125 μg/kg) by gavage for 35 consecutive days in 2014–2015, and a 2-ml blood sample was taken from each treated rat. Concentrations of BPA and NP in the blood were determined using the HPLC-fluorescence detection method. The sperm are produced in the epididymis and vas deferens, and they swim up in Ham’s F10 solution, and, then, various parameters were evaluated using an invert microscope, and they included the count, motility, and morphology of the sperm.ResultsThe weight of the testes and prostate in the rats receiving BPA and NP treatment showed significant decreases compared to the control group. Similarly, NP created higher concentration than BPA in the serum (e.g., 5.48 ± 0.65 vs. 1.36 ± 0.25, at 125 μg/kg). Compared to the control group, dose-dependent significant decreases in count and motility in the sperm were observed following the administration of BPA (25 and 125 μg/kg) and NP (all three doses). Morphologic aspects of the rats’ sperm were changed in various doses of BPA and NPConclusionsAccording to our findings, BPA and NP induced dose-dependent toxic effects on various parameters, i.e., sperm toxicity, weight of the testes, and weight of the prostate gland.

Mechanism of nonylphenol-induced neurotoxicity in F1 rats during sexual maturity

The purpose of this study was to examine whether gestational and lactational exposure to environmental endocrine disrupting chemical, nonylphenol (NP), in pregnant dams would lead to the alterations in hormone levels in the body, apoptosis and glial fibrillary acidic protein (GFAP) in hippocampus during weaning and sexual maturity periods in pups of rats. Dams were gavaged with NP at dose levels of 25mg/kg/day (low dose), 50mg/kg/day (middle dose), 100mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 6 to postnatal day (PND) 21. At PND 21, serum testosterone (TT) level significantly decreased in the 50, 100mg/kg NP-treated groups compared with the control (p < 0.01). Serum estradiol (E2) level was increased with the increase in the NP concentration; a dose-effect relationship was revealed (r = 0.462, p < 0.01). At both PND 21 and PND 60, pups exposed to 100mg/kg/day NP had an obviously higher apoptotic rate than control did. We observed a significant positive correlation between the dose of NP and the apoptotic rate (r = 0.836, p < 0.05). The number of GFAP-positive cells in rat hippocampus and integral optical density (IOD) of 100mg/kg/day NP-treated group were much higher than the control group. GFAP mRNA expressions increased at high dose (100mg/kg/day) (p < 0.05), and positive correlations between the GFAP mRNA expressions and NP level was observed (r = 0.586, 0.737, p < 0.05). Both the number of growth-associated protein (GAP)-43 positive cells and IOD were much lower at high dose (100mg/kg/day) than the control at both PND 21 and PND 60 (p < 0.05). The number of GAP-43 positive cells was negatively correlated with the NP exposure dose (r = - 0.562, - 0.649, p < 0.05) at these two time points. GAP-43 mRNA expressions in the hippocampus of pups decreased dramatically at high dose (100mg/kg/day) at both PND 21 and PND 60 compared with the control (p < 0.05). High exposure to NP might inhibit neuronal development and differentiation as indicated by the reduction of the neurotrophic factor GAP-43.

Histopathology and Histomorphometric Investigation of Bisphenol A and Nonylphenol on the Male Rat Reproductive System.

Background:Bisphenol A (BPA) and nonylphenol (NP) have harmful effects on the endocrine system of humans and animals.Aim:We sought to investigate the effect of three doses of BPA and NP on the reproductive parameters of rats.Materials and Methods:Adult Wistar male rats weighing 150–200 g were used for a consecutive 35-day study. BPA and NP were given as gavage in three doses (5, 25, and 125 μg/kg). At the end of the study, the rats were anesthetized and 2 ml blood sample was obtained from the auxiliary venous plexus for the assessment of sex hormone levels. The testes were removed and kept in 10% formalin for the histomorphometric and histopathologic analyses.Results:BPA and NP significantly decreased the body weight of the animals compared to the controls (P < 0.05). The seminiferous tubule diameter and thickness of the seminiferous epithelium were significantly decreased in the groups receiving BPA and NP compared to the control (P < 0.05). The number of seminiferous tubules in every experimental group increased, except for the highest dose of NP (125 μg/kg), which showed a significant difference compared to the controls (P < 0.05). The number of spermatocytes and spermatogonia (54.97 ± 5.824, 35.78 ± 3.956, respectively) in the group receiving NP (125 μg/kg) was significantly decreased compared to the other groups. Serum levels of luteinizing hormone, Follicle stimulating hormone, and testosterone did not show any significant change compared to the controls.Conclusion:Based on the results, all three doses of BPA and NP significantly produced weight loss, as well as destruction of the testis tissue and impairment of the spermatogenesis.

A mechanism of male germ cell apoptosis induced by bisphenol-A and nonylphenol involving ADAM17 and p38 MAPK activation.

Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA) and Nonylphenol (NP) induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1) to determine whether BPA and NP induce ADAM17 activation; and 2) to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg) induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α) ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation) of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis.

Alkylphenolic contaminants in the diet: Sparus aurata juveniles hepatic response

A wide range of endocrine disrupter chemicals can mimic steroid hormones causing adverse health effects. Nonylphenol (NP) and t-octhylphenol (t-OP) are man-made alkylphenolic environmental contaminants possessing controversial endocrine disruption properties. This study has investigated the effects of NP and t-OP enriched diets on hepatic tissue and biotransformation activities in the liver. To this aim, sea bream juveniles were fed with commercial diet enriched with three different doses of NP (NP1: 5mg/kg bw, NP2: 50mg/kg bw and NP3: 100mg/kg bw) or t-OP (t-OP1: 5mg/kg bw, t-OP2: 50mg/kg bw and t-OP3: 100mg/kg bw) for 21days. A significant increase of the hepatosomatic index was observed in NP1 and t-OP1. Alteration of liver morphology was observed in both NP and t-OP exposed juveniles although the most altered endpoints were observed in t-OP2 with 100% of tissue degeneration. Ethoxyresorufin-O-deethylase activity was significantly inhibited by NP and t-OP (p<0.05), while catalase activity was significantly induced, at both doses. A different pattern of protein expression of different isoforms of both vitellogenin and zona radiata protein was evidenced within the treatments. In addition, a significant increase in the abundance of the stress induced heat shock protein 70 gene in the liver of t-OP2 fish and a significant increase in the abundance of the estrogen induced cathepsin D gene in the liver of NP1 and t-OP2 fish, were observed. Finally, estradiol-17β (E2) and testosterone (T) plasma levels and E2/T showed significantly different patterns in NP and t-OP exposed against control fish.

Nonylphenol induces apoptosis via mitochondria- and Fas-l-mediated pathways in the liver of adult male rat

Nonylphenol (NP) is an environmental contaminant known to possess estrogenic properties. Humans are constantly exposed to NP by contaminated water and food products. In the present study we sought to investigate whether treatment with low doses of NP induces apoptosis in the liver of adult rats. Rats were administered with NP by oral gavage at the doses of 15,150 and 1500μg/kg body weight per day for 45days. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assayed. Apoptosis-related proteins namely cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l, and expression of bcl-2 mRNA and bax mRNA were examined in the liver. Levels of AST and ALT were increased in the treated rats. Western blot analysis revealed elevation in the levels of cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l in the liver of NP-treated rats. Decreased expression of bcl-2 mRNA (anti-apoptotic) and increased expression of bax mRNA (apoptotic) were observed in the liver of treated rats. Increased localization of caspase-3 in the hepatocytes and DNA damage were observed in the liver of treated rat. It is concluded that NP induces apoptosis in liver involving both mitochondria-dependent and Fas–Fas-l pathways and thereby, leading to hepatic damage in rats.

Effects of nonylphenol on the production of progesterone on the rats granulosa cells

We investigated the effects of nonylphenol (NP) on release of progesterone (PG) by granulosa cells (GCs) of rats in vitro and in vivo. First, GCs were treated with different doses of NP for 2-24 h alone or with human chorionic gonadotropin (hCG). Maximal PG secretion at 8 h noted, GCs were treated for 2 h with hCG, 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), forskolin, A23187, nifedipine, and pregnelonone to evaluate the NP effects on PG steroidogenesis. Results indicated that all of chemicals except nifedipine stimulated the PG release compared to vehicle, but the stimulatory effects could not be enhanced by different doses of NP. Second, GCs were isolated to react with hCG, 8-Br-cAMP and PD98059 after the immature female rats gavaged with different doses of NP (ONP) for 7 days. PG released significantly when rats treated with oral NP 100 compared to 0 µg/kg/day. Third, GCs collected from the female offspring of mother rats which gavaged with NP 100 µg/kg/day for 21 days during pregnancy (MONP) reacted with different doses of chemicals. The results showed that PG release in the presence of chemicals was significantly higher in ONP and MONP groups; however, this stimulation was not noted by dose-dependent. The plasma concentration of PG was higher in ONP (100 µg/kg/day) and the offspring of MONP groups. The steroidogenic acute regulatory (StAR) protein expressed higher in all three groups by Western blotting. This study results indicated that low dose of NP stimulated PG release in rat GCs by activation of StAR protein.