Linking pesticide exposure to neurodegenerative diseases: An in vitro investigation with human neuroblastoma cells.

Although many organochlorine pesticides (OCPs) have been banned or restricted because of their persistence and linkage to neurodegenerative diseases, there is evidence of continued human exposure. In contrast, registered herbicides are reported to have a moderate to low level of toxicity; however, there is little information regarding their toxicity to humans or their combined effects with OCPs. This study aimed to characterize the mechanism of toxicity of banned OCP insecticides (aldrin, dieldrin, heptachlor, and lindane) and registered herbicides (trifluralin, triallate, and clopyralid) detected at a legacy contaminated pesticide manufacturing and packing site using SH-SY5Y cells. Cell viability, LDH release, production of reactive oxygen species (ROS), and caspase 3/7 activity were evaluated following 24 h of exposure to the biocides. In addition, RNASeq was conducted at sublethal concentrations to investigate potential mechanisms involved in cellular toxicity. Our findings suggested that aldrin and heptachlor were the most toxic, while dieldrin, lindane, trifluralin, and triallate exhibited moderate toxicity, and clopyralid was not toxic to SH-SY5Y cells. While aldrin and heptachlor induced their toxicity through damage to the cell membrane, the toxicity of dieldrin was partially attributed to necrosis and apoptosis. Moreover, toxic effects of lindane, trifluralin, and triallate, at least partially, were associated with ROS generation. Gene expression profiles suggested that decreased cell viability induced by most of the tested biocides was related to inhibited cell proliferation. The dysregulation of genes encoding for proteins with anti-apoptotic properties also supported the absence of caspase activation. Identified enriched terms showed that OCP toxicity in SH-SY5Y cells was mediated through pathways associated with the pathogenesis of neurodegenerative diseases. In conclusion, this study provides a basis for elucidating the molecular mechanisms of pesticide-induced neurotoxicity. Moreover, it introduced SH-SY5Y cells as a relevant in vitro model for investigating the neurotoxicity of pesticides in humans.

Un plaguicida en el franquismo: comunicación de riesgos tóxicos en España, 1945-1975 / A pesticide in Franco's regime: communicating toxic risks in Spain, 1945-1975

Resumen En este trabajo se analizan las representaciones de los riesgos tóxicos del hexaclorociclohexano, un ingrediente activo de plaguicidas de uso común en los campos españoles durante el franquismo. Se hace énfasis en las prácticas que visibilizaron e invisibilizaron dichos riesgos en España entre 1945 y 1975, buscando establecer los actores que las fomentaron y los medios que emplearon. Desde la perspectiva de la agnotología, se analizan los procesos de creación de ignorancia e incertidumbre relacionadas con este compuesto. Asimismo, se examinan las estrategias retóricas utilizadas para abordarlos. Para ello se utilizan tres fuentes primarias principales: la revista de agronomía dirigida a expertos Boletín de patología vegetal y entomología agrícola, la revista dirigida a agricultores Agricultura y el periódico ABC.

Abstract This work analyzes the representations of the toxic risks of hexachlorocyclohexane, an active ingredient of many pesticides commonly used in Spanish fields during Franco's regime. Emphasis is placed on the practices that visibilized and invisibilized these risks, seeking to establish the actors that promoted them and the mechanisms they used. From the perspective of agnotology, I analyze the generation of ignorance and uncertainty related to this compound. Likewise, I examine the most prevalent rhetorical strategies used in print sources. To do so, I consulted three main primary sources: Boletín de patología vegetal y entomología agrícola, an agronomy journal for experts; Agricultura, a magazine for farmers, and ABC, a newspaper.

Analysis of serum levels of organochlorine pesticides and related factors in Parkinson's disease.

BACKGROUND: There is evidence that environmental factors contribute to the onset and progression of Parkinson's disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of developing PD. However, few studies have investigated the association between specific pesticides and PD, especially in China, which was one of the first countries to adopt the use of pesticides. METHODS: In this study, serum levels of 19 pesticides were measured in 90 patients with PD and 90 healthy spouse controls. We also analyzed the interaction between specific pesticides and PD. In addition, the association between pesticides and clinical features of PD was also investigated. Finally, we investigated the underlying mechanism of the association between pesticides and PD. RESULTS: Serum levels of organochlorine pesticides, which included α-hexachlorocyclohexane (HCH), ß-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p'-dichlorodiphenyltrichloroethane and o,p'-dichloro-diphenyl-trichloroethane were higher in PD patients than controls. Moreover, α-HCH and propanil levels were associated with PD. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. In SH-SY5Y cells, α-HCH and propanil increased level of reactive oxygen species and decreased mitochondrial membrane potential. Furthermore, propanil, but not α-HCH, induced the aggregation of α-synuclein. CONCLUSIONS: This study revealed that elevated serum levels of α-HCH and propanil were associated with PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. Moreover, propanil, but not α-HCH, induced the aggregation of α-synuclein. Further research is needed to fully elucidate the effects of pesticides on PD.

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by ß-Hexachlorocyclohexane-Activated Signaling Pathways.

The ß-isomer of hexachlorocyclohexane (ß-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of ß-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating ß-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting ß-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from ß-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.

Regional human health risk assessment of cadmium and hexachlorocyclohexane for agricultural land in China.

Widespread pollution of agricultural soil is posing great risks to food safety and human health. The absence of human health-based Generic Assessment Criteria (GAC) for agricultural land means Chinese farmers struggle to manage these risks efficiently and effectively. Cadmium (Cd) and hexachlorocyclohexane (HCH), two of the most concerned contaminants, demonstrate threshold toxicity meaning that background exposure (MDIoral) is considered when deriving soil Generic Assessment Criteria (GAC). The CLEA (Contaminated Land Exposure Assessment) model was used to derive GAC for Cd and HCH that reflect differences in diet and soil characteristics across 19 provinces/cities. For both cadmium and alpha-HCH, Sichuan had the lowest GAC of 0.379 mg kg-1 and 0.0136 mg kg-1, respectively, resulting from its significant high MDIoral values, which are approximately six to nine times larger than the average MDIoral for all the 19 provinces/cities. Jiangxi province had the highest GAC of 1.230 mg kg-1 and 0.0866 mg kg-1, respectively, for cadmium and alpha-HCH, caused by its notable low MDIoral values and low vegetable consumption rate. Human health risk assessment based on regional GAC for Cd revealed that agricultural land with very high to high risks is located in southern China, while very low-risk land is located in northern China. For HCH, alpha- and gamma-HCH pose negligible health risks, but beta-HCH poses some health risk in some of the provinces/cities. When applying the regional GAC for beta-HCH, agricultural land in Beijing and Sichuan posed the highest risk, and those in Heilongjiang and Jiangxi had the lowest risk. This reflects the significant influence of background and vegetable consumption pathway on the GAC. Regional GACs could simplify and speed up risk assessment of agricultural land in different regions of China, by avoiding the need to calculate site-specific assessment criteria, thus saving time and money by avoiding over or under remediation.

Wood preservatives in children's wooden toys from China: Distribution, migration, oral exposure, and risk assessment.

A total of 90 wooden toys were collected, and six wood preservatives (chlorophenols and lindane) were analyzed by using gas chromatography-tandem mass spectrometry to assess the exposure risk of children to wood preservatives through oral contact with wooden toys. The detection rates of six preservatives ranged from 2.2% to 22.2%. The contents of the preservatives ranged from 0.6 µg/kg to 9.6 µg/kg. 2,4-Dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) had higher detection rates and contents than other preservatives. Thus, their migration behaviors from toys to saliva were further investigated. In 11 positive samples, the max migration ratios of 2,4-DCP and 2,4,6-TCP ranged from 7.1% to 20.3% and from 11.1% to 24.8%, respectively. For children aged 3-36 months, the daily average 2,4-DCP exposure level associated with wooden toys ranged from 2.7 pg/(kg day) to 46.9 pg/(kg day), and the daily average 2,4,6-TCP exposure ranged from 3.6 pg/(kg day) to 69.4 pg/(kg day). The contribution to exposure provided by the saliva mobilization pathway was more than that provided by the ingestion of scraped-off toys, and the exposure level of 2,4,6-TCP was greater than that of 2,4-DCP. The max hazard quotient for 2,4-DCP was 1.9 × 10-4, and the max cancer risk for 2,4,6-TCP was 1.2 × 10-9. The above results indicated that although wood preservatives were distributed in wooden toys, exposure arising from directly mouthing these materials currently does not pose unacceptable risks to children.

Transcriptional response of zebrafish larvae exposed to lindane reveals two detoxification genes of ABC transporter family (abcg5 and abcg8).

Lindane is a highly toxic organochlorine pesticide and widely exist in water with harmful effects on fish. Although some genes have been found to be regulated by lindane in fish, the transcriptional response of fish exposed to lindane is still unknown. In this research, the transcriptional changes of zebrafish larvae exposed to 0.2 mg/L lindane from 96 to 120 hpf were studied by RNA sequencing. Our transcriptome identified 554 up-regulated and 118 down-regulated genes and the differentially expressed genes were closely related to the neuromast development, RNA silencing genes, ion transport, and response to estrogen. In addition, we characterized two sensitive and novel lindane-induced ABCG (ATP binding cassette G subfamily) transporter genes- abcg5 and abcg8. Abcg5 and abcg8 genes are located on chromosome 13 of zebrafish and contain 1956/2024 bp open reading frame. The polypeptide deduced by CDS amplification contains 652/676 amino acids and has most of the functional domains and key residues defined in human and mouse ABCG5/Abcg5 or ABCG8/Abcg8. Only when the co-expression of Abcg5 and Abcg8 enable them to transport to the cell membrane surface in 293T cells. In addition, lindane can induce the transcriptional expression of abcg5 and abcg8 genes, and overexpression of Abcg5 and Abcg8 significantly reduced the toxicity of lindane to zebrafish larvae, which means that zebrafish Abcg5 and Abcg8 are potential efflux transporters of lindane. Therefore, these findings provide useful insights for further understanding the zebrafish larvae's transcriptional response and detoxification ability after acute exposure to lindane.

Serum levels of Organochlorine Pesticides and Breast Cancer Risk in Iranian Women.

Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), ß-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.

Chronic prostatitis/chronic pelvic pain syndrome increases susceptibility to seizures in rats and alters brain levels of IL-1ß and IL-6.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a result of interplay between psychological, immune, neurological and genetic factors, manifested by variety of urological, as well as brain-related symptoms. However, its relation with brain excitability has not been addressed. herefore, our aim was to assess susceptibility to seizures in rats with CP/CPPS. We induced CP/CPPS in adult rats by intraprostatic injection of 3% λ-carrageenan. Sham operated rats served as controls (0.9% NaCl, Sham). On day 7 upon injection, rats were treated with lindane (4 mg/kg) and observed for convulsive behavior (seizure incidence, latency and severity) and EEG manifestations (number and duration of ictal periods). Interleukin levels (IL-1ß and IL-6) were measured in prostate, hippocampus, thalamus and cerebral cortex. Scrotal skin mechanical pain thresholds were determined and prostates were histologically evaluated. Animals with CP/CPPS showed significantly higher incidence, decreased latency time and augmented severity of lindane-induced seizures compared with Sham group. EEG revealed increased number of ictal periods in CP/CPPS rats. Higher levels of IL-1ß and IL-6 were determined in the thalamus and cortex in CP/CPPS animals vs. Sham. IL-1ß level was higher and IL-6 was lower in prostates from CP/CPPS animals comparing to Sham. CP/CPPS development was verified by histological findings of nonbacterial inflammation in the prostates, as well as by significantly decreased scrotal pain threshold in CP/CPPS animals. On the basis of this research, we concluded that CP/CPPS increases susceptibility to lindane-induced seizures in rats associated with increased level of IL-1ß and IL-6 in the cortex and thalamus.

Organochlorinated pesticides expedite the enzymatic degradation of DNA.

Extracellular DNA in the environment may play important roles in genetic diversity and biological evolution. However, the influence of environmental persistent organic contaminants such as organochlorinated pesticides (e.g., hexachlorocyclohexanes [HCHs]) on the enzymatic degradation of extracellular DNA has not been elucidated. In this study, we observed expedited enzymatic degradation of extracellular DNA in the presence of α-HCH, ß-HCH and γ-HCH. The HCH-expedited DNA degradation was not due to increased deoxyribonuclease I (DNase I) activity. Our spectroscopic and computational results indicate that HCHs bound to DNA bases (most likely guanine) via Van der Waals forces and halogen bonds. This binding increased the helicity and accumulation of DNA base pairs, leading to a more compact DNA structure that exposed more sites susceptible to DNase I and thus expedited DNA degradation. This study provided insight into the genotoxicity and ecotoxicity of pesticides and improved our understanding of DNA persistence in contaminated environments.

Bioaccumulation and human health risks of OCPs and PCBs in freshwater products of Northeast China.

The levels and spatial distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in freshwater products from Northeast China were investigated by gas chromatography coupled to isotope dilution high-resolution mass spectrometry. All samples were on-spot sampled from main production regions of freshwater products in Northeast China, and these samples were used to systematically assess the potential health risks of OCPs and PCBs associated with consumption of these fishery products. Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexane (HCHs), hexachlorobenzene (HCB) and PCBs were the major pollutants with 100% detection rates, and their levels ranged from 0.086 to 58, 0.038-3.3, 0.093-4.5 and 0.032-1.4 ng g-1 wet weight, respectively. The estimated dietary intakes of these contaminants were all below their corresponding acceptable daily intakes. Significant regional differences in the levels of OCPs and PCBs (P ≦ 0.001) were found in samples from Liaoning and Inner Mongolia. The results showed that the concentrations of targeted contaminants in aquatic products had species-specific characteristics, and the levels of targeted pollutants in Oncorhynchus mykiss and Eriocheir sienesis were significantly higher than those in other aquatic product species. Advisories on ten species of aquatic products suggested that consumption of Eriocheir sinensis, Oncorhynchus mykiss and Cyprinus carpio at a rate exceeding 15 meals per month would pose a cancer risk. A health risk assessment indicated that exposure to these pollutants through freshwater products consumption would cause a non-ignorable potential carcinogenic risk to humans.

Detection of lindane and 7,12-dimethylbenz[a]anthracene toxicity at low concentrations in a three-dimensional ovarian follicle culture system.

Exposure to environmental toxicants that target ovarian follicles can have long-lasting effects on women's reproductive health and health of the offspring. Experiments in rodents have contributed knowledge about the effects of individual toxicants on ovarian follicles. However, little is known about the effects of mixtures of toxicants on ovarian follicular health. We studied the combined effects of low, physiologically- and environmentally-relevant concentrations of toxicants on murine secondary ovarian follicles cultured in an encapsulated three-dimensional (3D) system. Exposure to lindane and 7,12-dimenthylbenz(a)anthracene (DMBA) led to decreased follicle survival, impaired development and compromised maturation in a concentration-dependent manner. DMBA showed a greater toxicity to cultured follicles compared to lindane. The mixtures of lindane and DMBA did not produce a synergistic toxic effect on follicles. Rather, ovarian follicles exposed to the mixtures showed survival and growth patterns similar to the follicles exposed to the same concentrations of individual toxicants. Our findings regarding follicle toxicity at such low concentrations help informing what might be overlooked when regulating environmental toxicants. The proposed 3D culture system allowed studying the effects of mixtures of environmental toxicants in a physiological setting, providing much needed information on how simultaneous exposure to multiple toxicants affects complex and sensitive biological structures, such as ovarian follicles.

Proteomic approaches to investigate age related vulnerability to lindane induced neurodegenerative effects in rats.

Proteomic studies were carried out in immature (3 week), adult (18 week) and aged (48 week) rats to understand the age dependent vulnerability to lindane induced neurodegeneration. 2-D and western blot analysis of protein extracts of hippocampus and substantia-nigra isolated from lindane treated rats (2.5 mg/kg; p.o. X 21 days) revealed marked dysregulation in the expression of proteins related to ubiquitin proteasome pathway, antioxidant activity, chaperones, energy metabolism, calcium homeostasis and proteins involved in neurodegeneration. These alterations were associated with marked increase in reactive oxygen species formation, lipid peroxidation, reduced glutathione content and antioxidant enzyme activities in lindane treated rats. Aged rats, in particular showed higher magnitude of alteration in these proteins when compared to immature or adult rats. Proteins involved in apoptosis and autophagy also showed marked alterations in their expression, particularly in the aged rats. Ultrastructural analysis revealed greater number of autophagic vesicle in hippocampus and substantia-nigra in treated aged rats. The data suggest that proteomic approaches could be used to investigate the vulnerability to lindane induced neurodegeneration in rats.

A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat or human term myometrium.

Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP's inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8×10-6M and 0.9×10-3M) and human myometrial contractions (EC50 16.3×10-6M and 1.1×10-3M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.

The pesticide Lindane induces dose-dependent damage to granulosa cells in an in vitro culture.

Lindane, which is one of the most persistent organochlorine pesticide contaminating the Aral Sea region, is associated with numerous pathologies of the female reproductive system, including infertility, due to its gap junction blocker activity. By using an in vitro model of reproductive toxicity consisting of mouse parietal granulosa cells (GCs) exposed to increasing concentrations of Lindane ranging from 1 to 100µM (L1; L10; L100), we aimed to ascertain the Lindane toxicity by evaluating the ultrastructure and expression of the cell death protein p53. GCs exposed to L1 showed an early sign of degeneration as chromatin marginalization and initial reduction of cell-to-cell contacts. Such effects increased at L10 with nuclear membrane invagination, cytoplasmic blebbing, reduction of microvilli and intercellular connections. L100 induced evident cellular damages with an extensive presence of vacuoles, cytoplasmic fragments, nuclear membrane vesiculation and abundant cellular debris. A dose-dependent increase of p53 expression was evident in the L1 and L10 groups but not in L100. These data provide evidence for a dose-dependent reproductive toxicity of the gap junction blocker Lindane, as seen in mouse GCs cultured in vitro by ultrastructural damage compatible with apoptosis. Since gap junctions may play a critical role in FSH-stimulated progesterone production, the ultrastructural damage here evidenced could explain the increase in the prevalence of reproductive pathologies and infertility in exposed women. Finally, this study provided a useful and repeatable model of reproductive toxicity in vitro, which is applicable to evaluate the detrimental effects of toxicants or the reversing effect of protective substances.

Organochlorine pesticides accumulation and breast cancer: A hospital-based case-control study.

The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. We conducted a hospital-based case-control study in 56 patients with breast cancer and 46 patients with benign breast disease. We detected the accumulation level of several organochlorine pesticides products (ß-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp'-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients using gas chromatography. Thereafter, we examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, we analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Our data showed that breast cancer patients suffered high accumulation levels of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp'-dichlorodiphenyldichloroethane were risk factors for breast cancer. Our results provide new evidence on etiology of breast cancer.

Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice.

Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and ß-hexachlorocyclohexane (ß-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and ß-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human.

Organochlorine pesticides in canned tuna and sardines on the Serbian market.

The aim of this study was to determine the level of organochlorine (OC) pesticides in 57 samples of canned tuna and 31 samples of canned sardines in vegetable oil, collected from supermarkets in Serbia. OC pesticides α-HCH, ß-HCH, δ-HCH, dichlorodiphenyltrichloroethane (DDT), DDE, DDD, dielderin, endosulfane I, endosulfane II, endosulan sulfate, endrin, endrin ketone, heptachlor, heptachlor epoxide, lindane, aldrin, metoxichlor, cis-chlordane and trans-chlordane were determined using a GS-MS method. The highest concentrations (µg kg-1, arithmetic means) in canned tuna were for δ-HCH (60.6 ± 97.0) and p, p´-DDT (55.0 ± 25.1), while the corresponding values in canned sardines were for δ-HCH (90.7 ± 102.7) and endosulfane II (78.0 ± 145.9). Mean level for the sum of endosulfans was above the maximum limit in canned sardines (85.0 µg kg-1). Also, dieldrin (39.7 µg kg-1) was measured above the ML.

Chemopreventive Agents Attenuate Rapid Inhibition of Gap Junctional Intercellular Communication Induced by Environmental Toxicants.

Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity.