Bisphenol A and polycystic ovary syndrome in human: A systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved. OBJECTIVE: To investigate the association between exposure to BPA and PCOS. SEARCH STRATEGY: Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases. SELECTION CRITERIA: Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS. DATA COLLECTION AND ANALYSIS: Following PRISMA guidelines, study characteristics and relevant data were extracted. MAIN RESULTS: Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present. CONCLUSIONS: Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.

Exposure to Phenols, Phthalates, and Parabens and Development of Metabolic Syndrome Among Mexican Women in Midlife.

Background: Evidence suggests exposure to endocrine-disrupting chemicals (EDCs) can influence Metabolic Syndrome (MetS) risk in adults, but it is unclear if EDCs impact women during midlife. We examined if EDCs measured in adult women were predictive of MetS and its components 9 years later. Methods: We measured urinary phthalate metabolites, phenols, and parabens collected in 2008 among 73 females from the ELEMENT study. MetS and its components (Abdominal Obesity, Hypertriglyceridemia, Cholesterolemia, Hypertension, and Hyperglycemia) were assessed in 2017. We regressed log-transformed EDC concentrations on MetS and MetS components using logistic regression, adjusting for age and physical activity. Results: At follow-up, the mean (SD) age was 46.6 (6.3) years; the prevalence of MetS was 34.3%. Sum of dibutyl phthalate metabolites (ΣDBP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP) were associated with an increased odds of hypertriglyceridemia. 2,5-dichlorophenol (2,5 DCP) and 2,4-dichlorophenol (2,4 DCP) were associated with increased odds of hypertriglyceridemia. The odds of hypertension were 4.18 (95% CI: 0.98, 17.7, p < 0.10) and 3.77 (95% CI: 0.76, 18.62, p < 0.10) times higher for every IQR increase in MCOP and propyl paraben, respectively. The odds of hyperglycemia were 0.46 (95% CI: 0.18, 1.17 p < 0.10) times lower for every IQR increase in the sum of di-2-ethylhexyl phthalate metabolites (ΣDEHP), and the odds of abdominal obesity were 0.70 (95% CI: 0.40, 1.21, p < 0.10) lower for every IQR increase in the concentration of triclosan. Conclusion: We found EDCs measured in 2008 were marginally predictive of hypertriglyceridemia and hypertension 9 years later. Results suggest that lower exposure to certain toxicants was related to lower markers of metabolic risk among midlife women.

Exposure to bisphenol A and breast cancer risk in northern Mexican women.

OBJECTIVE: To evaluate the association between BC and urinary concentrations of free-bisphenol A (BPA-F), the biological form of BPA, among women residing in Northern Mexico. METHODS: The population under study comprised 394 histologically confirmed BC cases and 404 age-matched controls. Women were interviewed face to face about their sociodemographic and reproductive characteristics. BPA-F was determined by high-pressure liquid chromatography equipped with a fluorescence detector (HPLC/FLD). Logistic regression models were used to estimate the adjusted BC risk in relation to BPA-F. RESULTS: BPA-F geometric mean was significantly higher among cases compared to controls (3.16 µg/L in cases and 2.47 µg/L in controls). A significant adjusted BC odds ratio of 2.31 (95% CI: 1.43-3.74) was estimated for the highest category of BPA-F compared to the lowest category. CONCLUSION: BPA-F may be an environmental cofactor of BC. Since this is the first report on BPA-F association with BC, our results need to be replicated.

Impact of BPA on behavior, neurodevelopment and neurodegeneration

Bisphenol A (BPA), a compound used in the manufacturing of plastics and epoxy resins, is an endocrine disruptor with significant adverse impact on the human's health. Here, we review the animal models and clinical studies as well as the molecular and cellular mechanisms that show that BPA alters the normal function of the reproductive system, metabolism, brain function and behavior and contributes to the development of certain neurodevelopmental disorders including autism spectrum and attention-deficit and hyperactivity disorders. BPA also causes aberrant cognitive function, behavioral disturbances, and neurodegenerative diseases, including Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis. It has recently been proposed that exposure to BPA may be associated with the development of certain neurodegenerative diseases and neurodevelopmental disorders; however, it is a line of research that is just emerging. This work aims to review the available information about the association between exposure to BPA and cognitive function, behavioral disturbances, neurodegenerative diseases (Parkinson�s Disease, Amyotrophic lateral sclerosis, Multiple Sclerosis), and neurodevelopmental disorders (Autism Spectrum and Attention-Deficit/Hyperactivity Disorders). Likewise, the molecular and cellular mechanisms that may be involved with these pathological conditions will be analyzed.

Efficacy of a phenol derivative, isopropyl vanillate, as an anti-inflammatory agent: A new small molecule inhibitor of COX and neutrophil migration.

Inflammation is the response of the body to noxious stimuli such as infections, trauma, or injury. Experimental studies have shown that vanillic acid has anti-inflammatory effects. The objective of this study was to investigate the anti-inflammatory and antipyretic properties of the derivative of vanillic acid, isopropyl vanillate (ISP-VT), in mice. The results of this study indicated that ISP-VT reduced paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin, bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, ISP-VT reduced recruitment of leukocytes and neutrophils and reduced its adhesion and rolling, and decreased myeloperoxidase enzyme activity (MPO), cytokine levels (tumor necrosis factor-α and interleukin-6), and vascular permeability. ISP-VT also significantly reduced the expression of cyclooxygenase-2 (COX-2) in subplantar tissue of mice. ISP-VT inhibited COX-2 selectively compared to the standard drug. Our results showed that although ISP-VT binds to COX-1, it is less toxic than indomethacin, as evidenced by MPO analysis of gastric tissue. Treatment with the ISP-VT significantly reduced rectal temperature in yeast-induced hyperthermia in mice. Our results showed that the main mechanism ISP-VT-induced anti-inflammatory activity is by inhibition of COX-2. In conclusion, our results indicate that ISP-VT has potential as an anti-inflammatory and antipyretic therapeutic compound.

Study of possible association between endometriosis and phthalate and bisphenol A by biomarkers analysis.

Endocrine disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) are substances that may interfere with the actions of endogenous hormones and may be associated with estrogen-related diseases such as endometriosis. This paper describes a case-control study to evaluate the relationship between endometriosis and phthalates and BPA exposure, through biomarkers analysis in urine. The biomarkers of exposure analyzed were metabolites mono-methyl phthalate, mono-isobutyl phthalate (MiBP), mono-butyl phthalate, mono-cyclohexyl phthalate, mono-(ethylhexyl) phthalate, mono-isononyl phthalate, mono-octyl phthalate (MOP), mono-benzyl phthalate and BPA. Urine samples were collected from women aged 18-45 years old. The Study group (n = 30) and Control group (n = 22) were composed of women using as criteria confirmation of endometriosis by videolaparoscopy surgery with histological diagnosis and the absence of the disease, respectively. The analytical method used liquid phase microextraction with determination by gas chromatography coupled to mass spectrometry. The concentrations of biomarkers were adjusted by the creatinine concentration in urine samples of the two groups. The values obtained for the Study Group were compared with the values obtained for the Control Group. The chi-square test and Odds Ratio were used to compare dichotomized phthalate metabolites and BPA metabolite by endometriosis. All nine metabolites were found in different concentrations in the urine samples in both groups The phthalate metabolites that had the highest concentrations, were MOP and MiBP, in which the values of 670 µg g-1 and 560 µg g-1, respectively. The relationship between endometriosis and the all grouped metabolites was evaluated, but was not statistically significant with a 95% CI [X2 (df = 1) = 1.471; p = 0.225]. However, odds ratio (95% confidence interval - CI) for MiBP, which was found at relatively high concentrations in the samples, by endometriosis was 1.929 (0.507-7.332). The food habits and gynecologic history were evaluated and no difference was found between groups. Although no evidences of causal link was found, this study contributes to show that other analysis must be done for evaluating the association between endometriosis and compounds suspected of being EDC.

Maternal bisphenol A exposure disrupts spermatogenesis in adult rat offspring.

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that is widely used in the manufacturing of plastics and inner linings of food cans. Previously, it was reported that BPA disturbed the sexual dimorphic nucleus of the hypothalamus and delaying the onset of puberty attributed to an estrogenic action. In addition, BPA during the perinatal period increased LH serum concentrations in male offspring of dams at doses below the reproductive NOAEL (No Observable Adverse Effect Level) based upon World Health Organization guidelines. Based upon these findings, the objective of this study was to (1) determine the effects of perinatal treatment with low doses of BPA on regulation of spermatogenesis in adult offspring and (2) elucidate molecular mechanisms involved in the pathogenesis of gonadal dysfunction. The expression of genes related to spermatogenesis was disrupted with adverse consequences on sperm production, reserves, and function. Both BPA treated groups exhibited reduction in sperm production and epithelial height of seminiferous tubules, accompanied by diminished integrity of the acrosome and plasma membrane, decreased mitochondrial activity and increased incidence of morphological abnormalities. The sperm transit time was also slower. However, only in the group receiving the higher BPA dose was transcript expression of genes affected (reduced Ar and increased Esr1). It is of interest that serum testosterone levels were elevated in the same group where Ar was decreased. Data suggest that exposure to low BPA doses during hypothalamic sexual differentiation period produces permanent deleterious effects on spermatogenesis in adulthood.

Exposure to bisphenol A: current levels from food intake are toxic to human cells.

In the present work, cell lines of different origin were exposed to BPA levels from food intake reported elsewhere. Specifically, we used an in vitro assay to determine cytotoxicity of BPA in three cell lines: MCF7 (breast cancer), PC3 (prostate cancer) and 3T3-L1 (mouse fibroblast). Cytotoxic effects were observed at concentrations higher than 50 µg/mL which is above the involuntary exposure level of BPA described before in fresh, canned and frozen foods and beverages. Furthermore, medial inhibitory concentrations (IC50) of 85.17 µg/mL and 88.48 µg/mL were observed for PC3 and 3T3-L1, respectively, and a slightly lower IC50 of 64.67 µg/mL for MCF7. These results highlight BPA's toxicity potential at current levels from food intake. The cell line-dependent divergent response to BPA reported herein is discussed.

Bisphenol S increases EZRIN expression and the detrimental effects induced by dehydroepiandrosterone in rat endometrium.

The use of Bisphenol S (BPS) was proposed as an alternative to Bisphenol A (BPA), a chemical employed in the production of polycarbonate plastics and epoxy resins. BPA is a xenoestrogen that affects normal physiology in several species. It was reported that BPS may also act as a xenoestrogen with harmful effects in the reproductive system. Here we studied the effects of BPS during the induction of a polycystic ovarian syndrome (PCOS)-like condition in rats. Animals were injected daily with vehicle, DHEA 60 mg/kg, BPS 1 µg/kg and DHEA-BPS, for 20 days. Cell apoptosis, cell proliferation, and EZRIN expression were analyzed by immunohistochemistry. We found an increase in PCNA expression, which correlates with cytoplasmic accumulation of the polarization marker, EZRIN, in the BPS treated groups. Additionally, the administration of BPS in the DHEA treated group augmented the stratification and number of "intraepithelial lumina" in the endometrial surface epithelium.

Long-term oral exposure to safe dose of bisphenol A in association with high-fat diet stimulate the prostatic lesions in a rodent model for prostate cancer.

BACKGROUND: Studies have shown that exposure to environmental chemicals known as endocrine disruptors can cause permanent changes in genital organs, such as the prostate. Among these environmental chemicals stands out bisphenol A (BPA). Another factor associated with prostate changes is the consumption of a high-fat diet. Although the relationship between the consumption of a high-fat diet and an increased risk of prostate cancer is well established, the mechanisms that lead to the establishment of this disease are not completely understood, nor the simultaneous action of BPA and high-fat diet. METHODS: Adult gerbils (100 days old) were divided in four groups (n = 6 per group): Control (C): animals that received a control diet and filtered water; Diet (D): animals that received a high-fat diet and filtered water; BPA: animals that received a control diet and BPA - 50 µg kg-1 day-1 in drinking water; BPA + Diet (BPA + D): animals that received a high-fat diet + BPA - 50 µg kg-1 day-1 in drinking water. After the experimental period (6 months), the dorsolateral and ventral prostate lobes were removed, and analyzed by several methods. RESULTS: Histological analysis indicated premalignant and malignant lesions in both prostatic lobes. However, animals of the D, BPA, and BPA + D groups showed a higher incidence and larger number of prostatic lesions; inflammatory foci were also common. Markers to assess prostate lesions, such as increased activation of the DNA repair system (PCNA-positive cells), androgen receptor (AR), and number of basal cells, confirmed the histology. However, serum levels of testosterone did not change under the experimental conditions. CONCLUSIONS: The results indicated that the methodology used was effective in generating metabolic changes, which directly compromised prostatic homeostasis. Diet and BPA appear to modulate the activation of the AR pathway and thereby optimize tumor establishment in the gerbil prostate.

Parental Concern about Environmental Chemical Exposures and Children's Urinary Concentrations of Phthalates and Phenols.

OBJECTIVES: To examine whether parents' concerns about environmental chemical exposures were associated with urinary phthalate and phenol concentrations in their school-age children. STUDY DESIGN: In a prospective cohort of 218 mother-child pairs from Cincinnati, Ohio (2010-2014), we measured 11 phthalate metabolites and 5 phenols in urine samples when children were age 8 years and used questionnaire data from caregivers. We estimated the covariate-adjusted percent difference in phthalates and phenols among children of parents who expressed concern about environmental chemical exposures compared with children whose parents did not. RESULTS: Concentrations of 4 phthalates, bisphenol S, and bisphenol A were lower among children whose parents expressed concern about environmental chemicals (n = 122) compared with those who did not (n = 96). Di-2-ethylhexyl phthalate metabolites, bisphenol S, and bisphenol A concentrations were 23% (95% CI -38, -5), 37% (95% CI -49, -21), and 13% (95% CI -26, 3) lower, respectively, among children whose parents expressed concern compared with those whose parents did not. Triclosan concentrations were 35% greater (95% CI -2, 87) among children whose parents expressed concern compared with children whose parents did not. CONCLUSIONS: Parental concern about environmental chemicals was associated with lower childhood urine concentrations of several phthalates and phenols; unexpectedly, parental concern was associated with greater triclosan concentrations. These results suggest that parental concern may be an important factor in mitigating children's phthalate and phenol exposures.

Lipidomic and Antioxidant Response to Grape Seed, Corn and Coconut Oils in Healthy Wistar Rats.

Specialty oils differ in fatty acid, phytosterol and antioxidant content, impacting their benefits for cardiovascular health. The lipid (fatty acid, phytosterol) and antioxidant (total phenolics, radical scavenging capacity) profiles of grapeseed (GSO), corn (CO) and coconut (CNO) oils and their physiological (triacylglycerides, total and HDL-cholesterol and antioxidant capacity (FRAP) in serum and fatty acid and phytosterol hepatic deposition) and genomic (HL, LCAT, ApoA-1 and SR-BP1 mRNA hepatic levels) responses after their sub-chronic intake (10% diet for 28 days) was examined in healthy albino rats. Fatty acid, phytosterol and antioxidant profiles differed between oils (p ≤ 0.01). Serum and hepatic triacylglycerides and total cholesterol increased (p ≤ 0.01); serum HDL-Cholesterol decreased (p < 0.05); but serum FRAP did not differ (p > 0.05) in CNO-fed rats as compared to CO or GSO groups. Hepatic phytosterol deposition was higher (+2.2 mg/g; p ≤ 0.001) in CO- than GSO-fed rats, but their fatty acid deposition was similar. All but ApoA-1 mRNA level increased in GSO-fed rats as compared to other groups (p ≤ 0.01). Hepatic fatty acid handling, but not antioxidant response, nor hepatic phytosterol deposition, could be related to a more efficient reverse-cholesterol transport in GSO-fed rats as compared to CO or CNO.

Perinatal Exposure to Bisphenol A or Diethylstilbestrol Increases the Susceptibility to Develop Mammary Gland Lesions After Estrogen Replacement Therapy in Middle-Aged Rats.

The development of the mammary gland is a hormone-regulated event. Several factors can dysregulate its growth and make the gland more susceptible to cellular transformation. Among these factors, perinatal exposure to xenoestrogens and hormone replacement therapy has been associated with increased risk of developing breast cancer. Here, we assessed the effects induced by estrogen replacement therapy (ERT) in ovariectomized (OVX) middle-aged rats and whether perinatal exposure to diethylstilbestrol (DES) or bisphenol A (BPA) modified these effects in the mammary gland. Pregnant rats were orally exposed to vehicle, 5 µg DES/kg/day, or 0.5 or 50 µg BPA/kg/day from gestational day 9 until weaning. Then, 12-month-old offspring were OVX and treated with 17ß-estradiol for 3 months. Morphological changes and the percentage of epithelial cells that proliferated or expressed estrogen receptor alpha (ESR1) and progesterone receptor (PR) were analyzed in mammary gland samples of 15-month-old animals. ERT induced lobuloalveolar hyperplasia and ductal cysts in the mammary gland of middle-aged rats, associated with a higher proliferation index of epithelial cells. Perinatal exposure to DES followed by ERT increased the number of cysts and induced the formation of fibroadenoma and ductal carcinoma in situ, without modifying the expression of ESR1 or PR. Also, after 3 months of ERT, BPA-exposed rats had a higher incidence of ductal hyperplasia and atypical lobular hyperplasia than animals under ERT alone. In conclusion, perinatal exposure to xenoestrogens increases the susceptibility of the mammary gland to develop cysts and hyperplastic lesions when confronted with ERT later in life.

Association of Bisphenol A Exposure with Breastfeeding and Perceived Insufficient Milk Supply in Mexican Women.

Introduction Estrogen inhibits lactation and bisphenol A (BPA) is a high production environmental estrogen. We hypothesize an inhibitory effect of BPA on lactation and aim to analyze the association between third trimester pregnancy urinary BPA and breastfeeding rates 1 month postpartum. Methods Odds ratios (OR) and 95 % confidence intervals (95 % CI) of breastfeeding and perceived insufficient milk supply (PIM) in relation to maternal peripartum urinary BPA concentrations were calculated in 216 mothers. Results 97.2 % of mothers in the lowest BPA tertile were breastfeeding at 1 month postpartum, compared to 89.9 % in highest (p = 0.01). Adjusted ORs (95 % CI) for not breastfeeding at 1 month were 1.9 (0.3, 10.7) and 4.3 (0.8, 21.6) for second and third BPA tertiles, respectively, compared to the lowest (p = 0.06, trend). 4.2 % reported PIM in the lowest BPA tertile, compared to 8.7 % in the highest (p = 0.03). Adjusted ORs (95 % CI) for PIM were 1.8 (0.4, 7.7) and 2.2 (0.5, 9.5), for the second and third BPA tertiles, respectively, compared to the lowest (p = 0.29, trend). Discussion These results suggest an association between maternal BPA exposure and decreased breastfeeding.

Combination of retinyl palmitate and UV-filters: phototoxic risk assessment based on photostability and in vitro and in vivo phototoxicity assays.

This study aimed to assess the phototoxic potential of combined UV-filters and retinyl palmitate (RP) in the presence or not of bemotrizinol (BMTZ), employing photostability and in vitro and in vivo phototoxicity assays. The formulations tested contained octocrylene (OCT), octyl methoxycinnamate (OMC), benzophenone-3 (BZP-3) and RP (photostable) or octocrylene (OCT), octyl methoxycinnamate (OMC), avobenzone (AVO) and RP (less photostable). Both formulations were supplemented with bemotrizinol. Photostability was evaluated by exposing, or not, formulations spread on a glass plate to UVA/UVB irradiation. The resulting products were quantified by HPLC analysis. In vitro phototoxicity of UV-filters and combinations were evaluated using 3T3 viable monolayer fibroblast cultures submitted, or not, to irradiation according to OECD TG 432. In vivo photoallergy and photoxicity were assessed by clinical studies (photopatch test). Photostability assays showed that UV-filter bemotrizinol was a better photostabilizer for RP/benzophenone-3 than for RP/avobenzone. The in vitro phototoxicity of the combination RP/avobenzone was reduced by bemotrizinol. Clinical studies did not indicate phototoxic or photoallergenic potentials in all formulations tested. It is concluded that the 3T3 NRU phototoxicity test may be considered a supplementary assay in formulation developments, since it can detect chemically unstable and potentially phototoxic combinations. However, extrapolation of in vitro positive results to human photopatch tests may be performed only to a limited extent.

Bisphenol A exposure is associated with decreased lung function.

OBJECTIVE: To examine the associations of bisphenol A (BPA) exposure with lung function measures and exhaled nitric oxide (FeNO) in children. STUDY DESIGN: We performed a cross-sectional analysis of a subsample of US children age 6-19 years who participated in the 2007-2010 National Health and Nutrition Examination Survey. We assessed univariate and multivariable associations of urinary BPA concentration with the predicted pulmonary function measures for age, sex, race/ethnicity and height (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], forced expiratory flow 25%-75%, and FEV1 divided by FVC) and with FeNO. RESULTS: Exposure and outcome data were available for 661 children. Median BPA was 2.4 ng/mL (IQR: 1.3, 4.1). In multivariable analysis, a larger urinary BPA concentration was associated with significantly decreased percent predicted forced expiratory flow 25%-75% (%FEF2575) (3.7%, 95% CI 1.0, 6.5) and percent predicted FEV1 divided by FVC (%FEV1/FVC) (0.8%, 95% CI 0.1, 1.7) but not percent predicted FEV1, percent predicted FVC, or FeNO. A child in the top quartile of BPA compared with the bottom quartile had a 10% decrease in %FEF2575 (95% CI -1, -19) and 3% decrease in %FEV1/FVC (95% CI -1, -5). CONCLUSIONS: BPA exposure was associated with a modest decrease in %FEF2575 (small airway function) and %FEV1/FVC (pulmonary obstruction) but not FEV1, FVC, or FeNO. Explanations of the association cannot rule out the possibility of reverse causality.

Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

OBJECTIVES: This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. MATERIALS AND METHODS: This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. RESULTS: Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. DISCUSSION: Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

Antioxidant effect of aqueous extract of propolis on hepatotoxicity induced by octylphenol in male rats / Efecto antioxidante del extracto acuoso de propóleos sobre la hepatotoxicidad inducida por el octilfenol en ratas macho

4-tertiary-octylphenol (4-tert-OP) is an alkylphenol that affects human health by stimulating free radical production. Aqueous propolis extract is a natural product rich in favonoids that have antioxidant activity. This study was designed to investigate the ability of aqueous propolis extract to reduce the hepatotoxicity induced by 4-tert-OP in male rats. Animals were assigned to 5 groups and treated for 6 weeks. Group 1: control; group 2: 100 mg 4-tert-OP/kg b.wt./day; group 3: 100 mg aqueous propolis extract /kg b.wt./day; group 4: 100mg 4-tert-OP/kg b.wt./day plus 100 mg aqueous propolis extract /kg b.wt./day; group 5: 100 mg 4-tert-OP/kg b.wt./day for 6 weeks followed by 100 mg aqueous propolis extract /kg b.wt./day for 6 weeks. Group 4-tert-OP signifcantly elevated AST, ALT, ALP, GGT, bilirubin, creatinine, urea, total lipids, total cholesterol, triglycerides, LDL-C and MDA with a signifcant decrease in total proteins, albumin, globulin, HDL-C, total antioxidant capacity, SOD, CAT and GST compared to control group. Administration of aqueous propolis extract either alone or combined with 4-tert-OP ameliorated the hepatotoxicity induced by 4-tert-OP. DNA fragmentation supported the deleterious effect of 4-tert-OP and the ameliorative effect of propolis on liver cellular proteins and enzymes. Histopathological fndings revealed the hepatotoxicity induced by 4-tert-OP and the protective effect of aqueous propolis extract. In conclusion, aqueous propolis extract could reduce the damage and toxicity effects on liver cells induced by 4-tert-OP.

El 4-terc-octilfenol (4-terc-OP) es un alquilfenol que afecta a la salud humana mediante la estimulación de la producción de radicales libres. El extracto acuoso de propóleos es un producto natural rico en favonoides que tienen actividad antioxidante. Este estudio fue diseñado para investigar la capacidad del extracto de propóleos de reducir la hepatotoxicidad inducida por el 4-terc-OP en ratas macho. Los animales fueron asignados a 5 grupos y tratados durante 6 semanas. Grupo 1: control; grupo 2: 100 mg de 4-terc-OP/kg/día; grupo 3: 100 mg de extracto de propóleos/kg/día; grupo 4: 100 mg de 4-terc-OP/ kg/día más 100 mg de extracto de propóleos/kg/día, grupo 5: 100 mg de 4-terc-OP/kg/día durante 6 semanas, seguidos de 100 mg de extracto de propóleos/kg/día durante 6 semanas. El grupo 4-terc-OP mostró niveles signifcativamente elevados de AST, ALT, ALP, GGT, bilirrubina, creatinina, urea, lípidos totales, colesterol total, triglicéridos, LDL-C y MDA, con una disminución signi-fcativa de proteínas totales, albúmina, globulina, HDL-C, la capacidad antioxidante total, SOD, CAT y GST, en comparación con el grupo control. La administración de extracto de propóleos, ya sea solo o combinado con 4-terc-OP redujo la hepatotoxicidad inducida por 4-terc-OP. Los estudios de fragmentación del ADN apoyan el efecto deletéreo observado por el tratamiento con 4-terc-OP y el efecto protector del extracto de propóleos, sobre las proteínas y las enzimas celulares hepáticas. Los resultados histopatológicos revelaron la hepatotoxicidad por 4-terc-OP y efecto protector inducido por el extracto de propóleos. En conclusión, el extracto de propóleos podría reducir el daño hepático y los efectos celulares de toxicidad en las células del hígado inducidos por 4-terc-OP.

Contribution of environmental pollutants to male infertily: a working model of germ cell apoptosis induced by plasticizers.

Bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA), 4-nonylphenol (NP) and di(2-ethylhexyl)phthalate (DEHP), and its metabolite mono-2-ethylhexyl phthalate (MEHP) are chemicals found in plastics, which act as endocrine disruptors (EDs) in animals, including human. EDs act like hormones in the endocrine system, and disrupt the physiologic function of endogenous hormones. Most people are exposed to different endocrine disruptors and concern has been raised about their true effect on reproductive organs. In the testis, they seem to preferentially attack developing testis during puberty rather than adult organs. However, the lack of information about the molecular mechanism, and the apparently controversial effect observed in different models has hampered the understanding of their effects on mammalian spermatogenesis. In this review, we critically discuss the available information regarding the effect of BPA, NP and DEHP/ MEHP upon mammalian spermatogenesis, a major target of EDs. Germ cell sloughing, disruption of the blood-testis-barrier and germ cell apoptosis are the most common effects reported in the available literature. We propose a model at the molecular level to explain the effects at the cellular level, mainly focused on germ cell apoptosis.