Genotoxicity of bisphenol AF in rats: Detrimental to male reproductive system and probable stronger micronucleus induction potency than BPA.

Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28-day multi-endpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF-treated groups (0.5, 5, and 50 µg/kg·bw/d), BPA group (10 µg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high-dose recovery group (BPAF-HR), oil recovery group (oil-R), ENU recovery group (ENU-R), and PBS recovery group (PBS-R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood-testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40-75-year-old non-smoking women in rural areas of southwest China.

This study evaluated the association between urinary cadmium (U-Cd) and blood Cd (B-Cd) and several biomarkers of renal dysfunction (α1 -microglobulin [α1 -MG], ß2 -microglobulin [ß2 -MG], N-acetyl-ß-d-glucosaminidase, metallothionein, retinol-binding protein and microalbumin [mALB]) and identified the biomarker(s) that was most closely correlated with U-Cd and B-Cd among female residents in rural areas of southwest China. U-Cd, creatinine (Cr), B-Cd and the above-mentioned six biomarkers in morning spot urine samples were measured from 288 randomly selected 40-75-year-old non-smoking women from non-polluted areas and Cd-polluted-areas. The lower 95% confidence limit of the benchmark dose (BMD) corresponding to the 5% (BMDL05 ) and 10% benchmark response (BMDL10 ) was calculated with assumed cut-off values of the 95th and 90th percentile. Among the investigated women, a significant positive association was found among mALB, ß2 -MG and U-Cd as well as B-Cd. By using the cut-off value of the 95th percentile, the BMDL05 /BMDL10 of U-Cd and B-Cd were 4.33/8.89 µg/g Cr for mALB and 1.35/2.77 µg/L for ß2 -MG, respectively. The BMDL05 /BMDL10 of U-Cd (B-Cd) was 2.73/5.60 µg/g Cr (1.00/2.05 µg/L) for mALB, if the cut-off value was set at the 90th percentile. Therefore, ß2 -MG and mALB in urine were good biomarkers for long-term environmental Cd exposure assessment among the six biomarkers studied for the study pool in southwest China. Our findings may help us to understand the association between nephrotoxicity and Cd exposure, and aid in the decision-making of authorities for environmental Cd pollution and public health.

[Effects of bamboo charcoal powder on lipid metabolism in hyperlipidaemic rats fed high fat diet].

OBJECTIVE: To evaluate of bamboo charcoal powder( BCP) on the lipid profile and mechanism in hyperlipidaemia model rats. METHODS: 40 male Sprague-Dawley( SD) animals of 4 weeks old were randomly assigned into five groups: the control group fed with low-fat diet; the model control group and the test group( 2. 81, 5. 62, 11. 24 g /kg). Each group gived BCP or distilled water correspondingly, the total administration duration was 90 consecutive days. After the blood samples were collected, liver, kidneys, and white adipose around bilateral epididymis and kidneys were excised and weighed. Serum biomarkers of liver and kidney function were detected. The activities of TC, TGand MDA, T-AOC, CAT, SOD of liver were determined by corresponding test kits according to the manufacturer's protocols. Livers were also further detected by macroscopic and microscopic examinations. RESULTS: After 90 days of treatment, the weight of rats more than 4 weeks, liver weight and percentage of body fat, serum AST, TG and VLDL, hepatic MDA, TG, TC and liver steatosis in the model control group was all increased compared with the negative control group, indicating that the model has been successfully built. It showed that the weight of rats, liver weight and white adipose weight, serum AST, TG and VLDL, hepatic MDA, TC and liver steatosis in the three dose group was all decreased. The hepatic SOD, CAT, T-AOC in the three dose groups were all increased. CONCLUSION: The BCP could reduce the accumulation of body fat, inmprove blood lipid and hepatic steatosis in hyperlipidemia model rats.

Acute and 28-day sub-acute oral toxicity evaluation of two dietary bamboo charcoal powders in Sprague-Dawley rats.

No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11.24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.

Exploring the Association of Leukocyte Telomere Length and Hearing Threshold Shifts of Adults in the United States.

Background: Although telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States. Methods: A total of 2,027 adults, aged 20-69 years, from the National Health and Nutrition Examination Surveys (NHANES, 1999-2002) were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure-tone average (PTA) for the better ear at ≥ 20 dB HL at frequencies 500, 1,000, 2,000, and 4,000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels. Results: The mean age of the participants was 40.60 ± 12.76 years, including 952 men (weighted, 48.67%) and 303 (weighted, 12.88%) participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a non-linear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted ß-21.45, 95% CI -37.28, -5.62; P = 0.008). When the T/S ratio exceeded0.82, MTL was not associated with high-frequency PTA (adjusted ß0.18, 95% CI -2.21, 2.57; P = 0.8809). Conclusion: Our findings revealed that MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner.

Serum polyunsaturated fatty acids and hearing threshold shifts in adults in the United States: A cross-sectional study.

Background: Few studies have evaluated the association between polyunsaturated fatty acids (PUFAs) and hearing levels. This study aimed to investigate the association between serum PUFAs and hearing threshold shifts in US adults. Methods: We investigated 913 adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Multivariate linear regression analyses were conducted to evaluate associations between PUFA and hearing threshold shifts. Results: Overall, 11 serum PUFAs were inversely associated with low-frequency thresholds, especially in men, and were positively related to high-frequency thresholds, particularly in the 40-59 years old cohort. Furthermore, some serum PUFAs were positively associated with both hearing threshold subgroups in women. Conclusion: Some PUFAs tend to be beneficial for low-frequency hearing status and detrimental to the high-frequency hearing threshold. The male sex may play a protective role in this association, while the female sex and middle age may be detrimental in the effect of PUFAs on hearing function.

Effects of atrazine on the proliferation and cytotoxicity of murine lymphocytes with the use of carboxyfluorescein succinimidyl ester-based flow cytometric approaches.

Atrazine (ATZ) is one of the most commonly applied herbicides worldwide. ATZ has been associated with adverse effects on the immune system; however, the mechanism of its immunotoxicity has not been completely elucidated. In this study, the immunotoxic effects of ATZ on murine splenic lymphocytes and magnetic bead-enriched NK cells were investigated in vitro with the use of carboxyfluorescein succinimidyl ester (CFDA-SE)-based flow cytometric approaches. Proliferation responses, NK cell activity, and T-cell early activation were determined with CFDA-SE loading, CFDA-SE/propidium iodide (PI) staining, and CD69+ expression, respectively. Cell apoptosis/cycle, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated using PI, 2',7'-dichlorodihydrofluorescein diacetate, and rhodamine 123, respectively. The intracellular expressions of apoptosis-related Bcl-2 and caspase-3 were analyzed through intracellular staining and flow cytometry. Results showed that proliferation and NK cell activity were suppressed by ATZ treatment. Such suppression might be associated with the cell apoptosis induced by increased ROS and declined MMP. The underlying mechanism might be the induced caspase-3 expression and decreased Bcl-2 expression. ATZ could elicit immunotoxic effects on murine lymphocytes; its presence in the environment might compromise immune function in organisms. The flow cytometric methods presented in this study should be further investigated in immunotoxicology.