Ajwa date flavonoids mitigate neutrophil migration and interferon-γ-induced renal injury by ultraviolet C radiation in rats.

Date was considered a high nutritional value fruit due to its high content of active ingredients. Frequent exposure to cosmetic radiations including UVC caused deleterious effects and tissue damage and organ affection. This study investigated the efficacy of Ajwa date extract (ADE) in protection against UVC-induced kidney injury in rats. Five groups of rats were included in this study. Group I: Rats were exposed to UVC radiation at a dose 5 kJ (1 h/day) for 28 days. Group II: Rats were pretreated orally with ADE (10 mg/kg/day) 1 h before exposure to UVC radiation with dose 5 kJ. Group III: Rats were pretreated with ADE (15 mg/kg) 1 h before exposure to UVC radiation. Group IV: Rats were exposed to UVC radiation then treated with ADE (10 mg/kg). Group V: Rats exposed to UV radiation then treated with ADE (15 mg/kg) after 1 h from exposure. Analyzing the active constituents of ADE by GC/MS showed that, quercetin, myricetin kaempferol, thymine, and catechol are the most active ingredients. Biochemical markers obtained showed that, serum 8-oxoguanine as marker for DNA damage was increased, and total antioxidant activity and glutathione reduced were decreased (p < 0.01), while neutrophil (p < 0.001), conjugated diene (p < 0.05), and interferon-γ (p < 0.01) were increased after exposure to UVC. However, all the parameters changed were reversed by ADE-treated rats compared with untreated; the higher dose was more effective and protective effect was better than treated effect. Kidney total proteins and reduced glutathione and procollagen levels were decreased while malondialdehyde was increased after exposure to UVC (p < 0.01). These abnormalities were normalized by ADE treatment and protected. It was concluded that, flavonoids from Ajwa extract protected against deleterious effects of UVC by enhancing antioxidant activities and reducing infiltration of neutrophils that caused kidney injury.

Evaluation of Cyto-genotoxicity of Perfluorooctane Sulfonate (PFOS) to Allium cepa.

Per- and polyfluoroalkyl substances (PFAS) have emerged as contaminants of global concern. Among several PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent and bioaccumulative compounds. We investigated the cyto-genotoxic potential of PFOS to Allium cepa root meristem cells. The A. cepa root tips were exposed to 6 different concentrations (1-100 mg L-1 ) of PFOS for 48 h. Reduction in mitotic index and chromosomal aberrations was measured as genotoxic endpoints in meristematic root cells. Exposure to PFOS significantly affected cell division by reducing the miotic index at higher concentrations (>10 mg L-1 ). The median effect concentration of PFOS to elicit cytotoxicity based on the mitotic index was 43.2 mg L-1 . Exposure to PFOS significantly increased chromosomal aberrations at concentrations >25 mg L-1 . The common aberrations were micronuclei, vagrant cells, and multipolar anaphase. The alkaline comet assay revealed a genotoxic potential of PFOS with increased tail DNA percentage at concentrations >25 mg L-1 . To our knowledge, this is the first study to report the cyto-genotoxic potential of PFOS in higher plants. Environ Toxicol Chem 2021;40:792-798. © 2020 SETAC.

Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline.

Endocrine-disrupting chemicals are ubiquitously present in our environment, but the mechanisms by which they adversely affect human reproductive health and strategies to circumvent their effects remain largely unknown. Here, we show in Caenorhabditis elegans that supplementation with the antioxidant Coenzyme Q10 (CoQ10) rescues the reprotoxicity induced by the widely used plasticizer and endocrine disruptor bisphenol A (BPA), in part by neutralizing DNA damage resulting from oxidative stress. CoQ10 significantly reduces BPA-induced elevated levels of germ cell apoptosis, phosphorylated checkpoint kinase 1 (CHK-1), double-strand breaks (DSBs), and chromosome defects in diakinesis oocytes. BPA-induced oxidative stress, mitochondrial dysfunction, and increased gene expression of antioxidant enzymes in the germline are counteracted by CoQ10. Finally, CoQ10 treatment also reduced the levels of aneuploid embryos and BPA-induced defects observed in early embryonic divisions. We propose that CoQ10 may counteract BPA-induced reprotoxicity through the scavenging of reactive oxygen species and free radicals, and that this natural antioxidant could constitute a low-risk and low-cost strategy to attenuate the impact on fertility by BPA.

Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans.

Chemicals that are highly prevalent in our environment, such as phthalates and pesticides, have been linked to problems associated with reproductive health. However, rapid assessment of their impact on reproductive health and understanding how they cause such deleterious effects, remain challenging due to their fast-growing numbers and the limitations of various current toxicity assessment model systems. Here, we performed a high-throughput screen in C. elegans to identify chemicals inducing aneuploidy as a result of impaired germline function. We screened 46 chemicals that are widely present in our environment, but for which effects in the germline remain poorly understood. These included pesticides, phthalates, and chemicals used in hydraulic fracturing and crude oil processing. Of the 46 chemicals tested, 41% exhibited levels of aneuploidy higher than those detected for bisphenol A (BPA), an endocrine disruptor shown to affect meiosis, at concentrations correlating well with mammalian reproductive endpoints. We further examined three candidates eliciting aneuploidy: dibutyl phthalate (DBP), a likely endocrine disruptor and frequently used plasticizer, and the pesticides 2-(thiocyanomethylthio) benzothiazole (TCMTB) and permethrin. Exposure to these chemicals resulted in increased embryonic lethality, elevated DNA double-strand break (DSB) formation, activation of p53/CEP-1-dependent germ cell apoptosis, chromosomal abnormalities in oocytes at diakinesis, impaired chromosome segregation during early embryogenesis, and germline-specific alterations in gene expression. This study indicates that this high-throughput screening system is highly reliable for the identification of environmental chemicals inducing aneuploidy, and provides new insights into the impact of exposure to three widely used chemicals on meiosis and germline function.

First Trimester Urinary Bisphenol and Phthalate Concentrations and Time to Pregnancy: A Population-Based Cohort Analysis.

Background: Increasing evidence suggests that exposure to synthetic chemicals such as bisphenols and phthalates can influence fecundability. The current study describes associations of first trimester urinary concentrations of bisphenol A (BPA), BPA analogs, and phthalate metabolites with time to pregnancy (TTP). Methods: Among 877 participants in the population-based Generation R pregnancy cohort, we measured first trimester urinary concentrations of bisphenols and phthalates [median gestational age, 12.9 weeks (interquartile range, 12.1, 14.4)]. We used fitted covariate-adjusted Cox proportional hazard models to examine associations of bisphenol and phthalate concentrations with TTP. Participants who conceived using infertility treatment were censored at 12 months. Biologically plausible effect measure modification by folic acid supplement use was tested. Results: In the main models, bisphenol and phthalate compounds were not associated with fecundability. In stratified models, total bisphenols and phthalic acid were associated with longer TTP among women who did not use folic acid supplements preconceptionally [respective fecundability ratios per each natural log increase were 0.90 (95% CI, 0.81 to 1.00) and 0.88 (95% CI, 0.79 to 0.99)]. Using an interaction term for the exposure and folic acid supplement use showed additional effect measure modification by folic acid supplement use for high-molecular-weight phthalate metabolites. Conclusions: We found no associations of bisphenols and phthalates with fecundability. Preconception folic acid supplementation seems to modify effects of bisphenols and phthalates on fecundability. Folic acid supplements may protect against reduced fecundability among women exposed to these chemicals. Further studies are needed to replicate these findings and investigate potential mechanisms.

Bisphenol and phthalate concentrations and its determinants among pregnant women in a population-based cohort in the Netherlands, 2004-5.

BACKGROUND: Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. OBJECTIVE: To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. METHODS: In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. RESULTS: Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]). CONCLUSION: Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust.

Urinary Phytoestrogen Concentrations Are Not Associated with Incident Endometriosis in Premenopausal Women.

BACKGROUND: Phytoestrogens have been associated with subtle hormonal changes, but their effects on endometriosis are largely unknown. OBJECTIVE: We assessed the association between urinary concentrations of phytoestrogens and incident endometriosis. METHODS: We included an operative sample of 495 premenopausal women aged 18-44 y undergoing laparoscopies and laparotomies at 14 clinical sites between 2007 and 2009 and a general population sample of 131 women from the same geographic area who were matched on age and menstruation status. Endometriosis in the surgical sample was assessed by surgical visualization (clinical gold standard), whereas disease in the general population sample was assessed with the use of a pelvic MRI. Urine concentrations of genistein, daidzen, O-desmethylangolensin, equol, enterodiol, and enterolactone were measured at baseline. Poisson regression with robust error variance was used to estimate the risk of an endometriosis diagnosis for each sample after adjusting for age and body mass index (in kg/m2). Separate models were run for each phytoestrogen. RESULTS: Overall geometric mean urine concentrations of phytoestrogens were as follows: genistein [88 nmol/L (95% CI: 72, 108 nmol/L)], daidzein [194 nmol/L (95% CI: 160, 236 nmol/L)], O-desmethylangolensin [4 nmol/L (95% CI: 3, 6 nmol/L)], equol [4 nmol/L (95% CI: 4, 6 nmol/L)], enterodiol [29 nmol/L (95% CI: 22, 38 nmol/L)], and enterolactone [355 nmol/L (95% CI: 395, 544 nmol/L)]. Geometric mean concentrations of phytoestrogens did not significantly differ by endometriosis status in either sample. Adjusted RRs for endometriosis ranged from 0.87 to 1.09 for the 6 phytoestrogens measured, with all CIs including a value ≥1. Phytoestrogens were not associated with the severity of endometriosis when restricting the analysis to women with moderate-to-severe disease per the revised American Society for Reproductive Medicine criteria. Furthermore, no associations were observed between self-reported high soy intake and endometriosis. CONCLUSIONS: Despite endometriosis being an estrogen-dependent disease, we found no evidence that urinary phytoestrogens were associated with a higher risk of an endometriosis diagnosis in either a sample of premenopausal women or in a surgical sample.

Thyroid hormone actions are temperature-specific and regulate thermal acclimation in zebrafish (Danio rerio).

BACKGROUND: Thyroid hormone (TH) is best known for its role in development in animals, and for its control of metabolic heat production (thermogenesis) during cold acclimation in mammals. It is unknown whether the regulatory role of TH in thermogenesis is derived in mammals, or whether TH also mediates thermal responses in earlier vertebrates. Ectothermic vertebrates show complex responses to temperature variation, but the mechanisms mediating these are poorly understood. The molecular mechanisms underpinning TH action are very similar across vertebrates, suggesting that TH may also regulate thermal responses in ectotherms. We therefore aimed to determine whether TH regulates thermal acclimation in the zebrafish (Danio rerio). We induced hypothyroidism, followed by supplementation with 3,5-diiodothyronine (T2) or 3,5,3'-triiodothyronine (T3) in zebrafish exposed to different chronic temperatures. We measured whole-animal responses (swimming performance and metabolic rates), tissue-specific regulatory enzyme activities, gene expression, and free levels of T2 and T3. RESULTS: We found that both T3 and the lesser-known T2, regulate thermal acclimation in an ectotherm. To our knowledge, this is the first such study to show this. Hypothyroid treatment impaired performance measures in cold-acclimated but not warm-acclimated individuals, whereas supplementation with both TH metabolites restored performance. TH could either induce or repress responses, depending on the actual temperature and thermal history of the animal. CONCLUSIONS: The low sensitivity to TH at warm temperatures could mean that increasing temperatures (that is, global warming) will reduce the capacity of animals to regulate their physiologies to match demands. We suggest that the properties that underlie the role of TH in thermal acclimation (temperature sensitivity and metabolic control) may have predisposed this hormone for a regulatory role in the evolution of endothermy.

Profiles of phytoestrogens in human urine from several Asian countries.

Intake of a diet rich in phytoestrogens has been associated with a decreased risk for hormone-dependent cancers in humans. Biomonitoring of phytoestrogens in human urine has been used to assess the intake of phytoestrogens. Although studies have reported phytoestrogen levels in urine specimens from the United States and Japan, little is known of human intake of phytoestrogens in other Asian countries. In this study we determined the concentrations of seven phytoestrogens, namely, enterolactone, enterodiol, daidzein, equol, O-desmethylangolensin (O-DMA), genistein, and coumestrol, in 199 human urine samples from three Asian countries, Vietnam (Hanoi and Ho Chi Minh), Cambodia (Phnom Penh), and India (Chennai and Kolkata), using a simple, sensitive, and reliable liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method. The residue levels of phytoestrogens in urine samples from the three Asian countries were compared with the concentrations in 26 urine samples from Japan (Ehime) and 16 urine samples from the United States (Albany), analyzed in this study. Among the phytoestrogens analyzed, isoflavones such as daidzein and genistein were predominant in urine samples from Vietnam; samples from Cambodia and India contained higher concentrations of enterolactone than isoflavones. Urinary concentrations of isoflavones in samples from Hanoi, Vietnam, were notably higher than the concentrations in samples from Cambodia, India, and the United States and similar to the concentrations in samples from Japan. The lowest concentrations of daidzein and the highest concentrations of enterolactone were found in urine samples from India. Concentrations of equol and O-DMA, which are microbial transformation products of daidzein (produced by gut microflora), were notably high in urine samples from Hanoi, Vietnam. The ratios of the concentration of equol or O-DMA to that of daidzein were significantly higher in samples from Hanoi than from Japan, indicating high biotransformation efficiency of daidzein by the population in Hanoi. High concentrations of equol, in addition to isoflavones, in urine have been linked to reduced breast cancer risk in previous studies, and, thus, the Vietnamese population may have potential protective effect against breast cancer. This study suggests that the dietary intake and profiles of phytoestrogens vary considerably, even among Asian countries.

Benzo[a]pyrene and total polycyclic aromatic hydrocarbons (PAHs) levels in vegetable oils and fats do not reflect the occurrence of the eight genotoxic PAHs.

Concentrations of polycyclic aromatic hydrocarbons (PAHs) were determined in 115 samples of olive oil (extra virgin olive oil, virgin olive oil, olive oil, pomace olive oil and blended olive oil), cooking oil (corn oil, sunflower oil, sesame oil, palm olein oil, soya oil, canola oil, mustard oil, peanut oil and mixed vegetable oil) and fat (butter and table margarine) collected from retail stores in Kuwait. Carcinogenic benzo[a]pyrene (BaP) was detected in 43% of the samples analyzed. Benz[a]anthracene and chrysene were detected in 37 and 45% of the samples, respectively, that did not contain BaP. Of the individual non-carcinogenic PAHs, naphthalene showed the highest mean concentration (14 microg kg(-1)), while for the carcinogenic PAHs, BaP (0.92 microg kg(-1)) and chrysene (0.87 microg kg(-1)) showed the highest mean values. Approximately 20% of the samples within the olive oil and cooking oil sub-categories exceeded the EU maximum tolerable limit for BaP, with the highest level of 6.77 and 11.1 microg kg(-1), respectively. For the fat sub-category, 9% of the samples exceeded the tolerance limit, with the highest level of 3.67 microg kg(-1). The Kuwaiti general population's dietary exposure to the genotoxic PAHs (PAH8: benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, dibenz[a,h]anthracene and benzo[ghi]perylene) was estimated to be 196 ng day(-1) (3.3 ng kg(-1) bw day(-1), assuming an average adult body weight of 60 kg). Results indicated that PAH8 and BaP(eq) (total sum benzo[a]pyrene equivalents) are more reliable measures of the concentrations of other carcinogenic PAHs in oil and fat samples, while BaP and PAHs alone are not good indicators of the occurrence or degree of contamination by carcinogenic PAHs in these food products.