Bisphenol A Effects on Neurons' Neurochemical Character in the Urinary Bladder Intramural Ganglia of Domestic Pigs.

Bisphenol A (BPA), a substance globally used to produce plastics, is part of many everyday items, including bottles, food containers, electronic elements, and others. It may penetrate the environment and living organisms, negatively affecting, among others, the nervous, immune, endocrine, and cardiovascular systems. Knowledge of the impact of BPA on the urinary bladder is extremely scarce. This study investigated the influence of two doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b.w./day) given orally for 28 days on the neurons situated in the ganglia located in the urinary bladder trigone using the typical double immunofluorescence method. In the study, an increase in the percentage of neurons containing substance P (SP), galanin (GAL), a neuronal isoform of nitric oxide synthase (nNOS-used as the marker of nitrergic neurons), and/or cocaine- and amphetamine-regulated transcript (CART) peptide was noted after BPA administration. The severity of these changes depended on the dose of BPA and the type of neuronal factors studied. The most visible changes were noted in the cases of SP- and/or GAL-positive neurons after administering a higher dose of BPA. The results have shown that oral exposure to BPA, lasting even for a short time, affects the intramural neurons in the urinary bladder wall, and changes in the neurochemical characterisation of these neurons may be the first signs of BPA-induced pathological processes in this organ.

A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice.

Introduction: Bisphenol A (BPA) is a substance belonging to the endocrine-disrupting chemicals, globally used in the production of polycarbonate plastics. It has been found that BPA enhances carcinogenesis, triggers obesity and exerts a pathogenic effect in several disorders, such as type 2 diabetes, asthma, or increased blood pressure. Recent studies have revealed, that BPA has a harmful impact on the kidneys function, therefore, the current research aimed to explore the specific molecular changes triggered in these organs after oral BPA exposure in mice. Materials and Methods: The experiment was carried out on 12 (3-month-old) female mice. Six mice served as controls. The other 6 mice were treated with BPA in the drinking water at a dose of 50 mg/kg b. w. for 3 months. Then animals were euthanized, the kidneys were collected, and extracted RNA was used to perform RNA-seq. Results: Applied multistep bioinformatics revealed 433 differentially expressed genes (DEGs) in the BPA-treated kidneys (232 upregulated and 201 downregulated). Additionally, 95 differentially expressed long-noncoding RNAs (DELs) were revealed in BPA samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that BPA exposure resulted in profound changes in several essential processes, such as oxidative phosphorylation, mitochondrial and ribosome function, or chemical carcinogenesis. Conclusion: The obtained novel results suggest that BPA has a harmful impact on the fundamental processes of the kidney and significantly impairs its function by inducing mitochondrial dysfunction leading to oxidative stress and reactive oxygen species production.

The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies.

Bisphenol A (BPA) is an environmental toxin widely used in the production of polycarbonate plastics. A correlation exists between BPA tissue contamination and the occurrence of pathological conditions, including cancer. First-passage detoxification of high BPA amounts in the liver promotes hepatotoxicity and morphological alterations of this organ, but there is a lack of knowledge about the molecular mechanisms underlying these phenomena. This prompted us to investigate changes in the liver transcriptomics of 3-month-old female mice exposed to BPA (50 mg/kg) in drinking water for 3 months. Five female mice served as controls. The animals were euthanized, the livers were collected, and RNA was extracted to perform RNA-seq analysis. The multistep transcriptomic bioinformatics revealed 120 differentially expressed genes (DEGs) in the BPA-exposed samples. Gene Ontology (GO) annotations indicated that DEGs have been assigned to many biological processes, including "macromolecule modification" and "protein metabolic process". Several of the revealed DEGs have been linked to the pathogenesis of severe metabolic liver disorders and malignant tumors, in particular hepatocellular carcinoma. Data from this study suggest that BPA has a significant impact on gene expression in the liver, which is predictive of the carcinogenic potential of this compound in this organ.

Influence of bisphenol A and its analog bisphenol S on cocaine- and amphetamine-regulated transcript peptide-positive enteric neurons in the mouse gastrointestinal tract.

Introduction: Bisphenol A (BPA) is used in large quantities for the production of plastics and is present in various everyday objects. It penetrates living organisms and shows multidirectional adverse influence on many internal organs. For this reason, BPA is often replaced in plastic production by other substances. One of them is bisphenol S (BPS), whose effects on the enteric nervous system (ENS) have not been explained. Methods: Therefore, the present study compares the influence of BPA and BPS on the number of enteric neurons immunoreactive to cocaine-and amphetamine-regulated transcript (CART) peptide located in the ENS of the stomach, jejunum and colon with the use of double immunofluorescence method. Results: The obtained results have shown that both bisphenols studied induced an increase in the number of CART-positive enteric neurons, and the severity of changes depended on the type of enteric ganglion, the dose of bisphenols and the segment of the digestive tract. The most visible changes were noted in the myenteric ganglia in the colon. Moreover, in the colon, the changes submitted by BPS are more noticeable than those observed after BPA administration. In the stomach and jejunum, bisphenol-induced changes were less visible, and changes caused by BPS were similar or less pronounced than those noted under the impact of BPA, depending on the segment of the gastrointestinal tract and ganglion type studied. Discussion: The results show that BPS affects the enteric neurons containing CART in a similar way to BPA, and the BPS impact is even stronger in the colon. Therefore, BPS is not neutral for the gastrointestinal tract and ENS.

Changes Caused by Bisphenols in the Chemical Coding of Neurons of the Enteric Nervous System of Mouse Stomach.

Bisphenol A (BPA), an organic chemical compound which is widely used in the production of plastics, can severely damage live organisms. Due to these findings, the plastic industry has started to replace it with other substances, most often with bisphenol S (BPS). Therefore, during the present investigation, with the use of double immunofluorescence labeling, we compared the effect of BPA and BPS on the enteric nervous system (ENS) in the mouse corpus of the stomach. The obtained results show that both studied toxins impact the amount of nerve cells immunoreactive to substance P (SP), galanin (GAL), vesicular acetylcholine transporter (VAChT is used here as a marker of cholinergic neurons) and vasoactive intestinal polypeptide (VIP). Changes observed under the impact of both bisphenols depended on the neuronal factor, the type of the enteric ganglion and the doses of bisphenols studied. Generally, the increase in the percentage of neurons immunoreactive to SP, GAL and/or VIP, and the decrease in the percentage of VAChT-positive neurons, was noted. Severity of changes was more visible after BPA administration. However, the study has shown that long time exposure to BPS also significantly affects the ENS.

Effects of the long-term influence of bisphenol A and bisphenol S on the population of nitrergic neurons in the enteric nervous system of the mouse stomach.

Bisphenol A (BPA) is an endocrine disruptor commonly used in the production of plastics. Due to its relatively well-known harmful effects on living organisms, BPA is often replaced by its various analogues. One of them is bisphenol S (BPS), widely used in the plastics industry. Until recently, BPS was considered completely safe, but currently, it is known that it is not safe for various internal organs. However, knowledge about the influence of BPS on the nervous system is scarce. Therefore, the aim of this study was to investigate the influence of two doses of BPA and BPS on the enteric nitrergic neurons in the CD1 strain mouse stomach using the double-immunofluorescence technique. The study found that both substances studied increased the number of nitrergic neurons, although changes under the impact of BPS were less visible than those induced by BPA. Therefore, the obtained results, for the first time, clearly indicate that BPS is not safe for the innervation of the gastrointestinal tract.

Changes in the Enteric Neurons Containing Selected Active Substances in the Porcine Descending Colon after the Administration of Bisphenol A (BPA).

Bisphenol A (BPA) is an endocrine disruptor widely distributed in the environment due to its common use in the plastics industry. It is known that it has a strong negative effect on human and animal organisms, but a lot of aspects of this impact are still unexplored. This includes the impact of BPA on the enteric nervous system (ENS) in the large intestine. Therefore, the aim of the study was to investigate the influence of various doses of BPA on the neurons located in the descending colon of the domestic pig, which due to similarities in the organization of intestinal innervation to the human gastrointestinal tract is a good animal model to study processes occurring in human ENS. During this study, the double immunofluorescence technique was used. The obtained results have shown that BPA clearly affects the neurochemical characterization of the enteric neurons located in the descending colon. The administration of BPA caused an increase in the number of enteric neurons containing substance P (SP) and vasoactive intestinal polypeptide (VIP) with a simultaneously decrease in the number of neurons positive for galanin (GAL) and vesicular acetylcholine transporter (VAChT used as a marker of cholinergic neurons). Changes were noted in all types of the enteric plexuses, i.e., the myenteric plexus, outer submucous plexus and inner submucous plexus. The intensity of changes depended on the dose of BPA and the type of enteric plexus studied. The results have shown that BPA may affect the descending colon through the changes in neurochemical characterization of the enteric neurons located in this segment of the gastrointestinal tract.

Environmental Pollution with Bisphenol A and Phthalates-A Serious Risk to Human and Animal Health.

Pollution of the natural environment is constantly increasing due to industrial development and progressive urbanization [...].

Hair Sample Analysis of Residents from Olsztyn, Northeastern Poland, to Evaluate Levels of Bisphenol S and Bisphenol A: A Pilot Study.

BACKGROUND Bisphenol A (BPA) and its analogue bisphenol S (BPS), widely utilized in numerous fields of industry, may seep into the environment and into human organisms. Hitherto, BPA was regarded as the bisphenol to which people were exposed to the greatest extent. As endocrine disruptors, bisphenols have negative effects on human health. Therefore, defining the levels of human exposure to these compounds is a key issue in toxicology. Hair analysis has been increasingly used for biomonitoring of bisphenols in humans, but information about the coexistence of BPA and BPS in human hair is extremely scarce. The present study aimed to analyze hair samples from 25 individuals from Olsztyn, northeastern Poland, to evaluate the levels of these 2 industrial pollutants. MATERIAL AND METHODS The method used in the research was liquid chromatography with a mass spectrometry technique. RESULTS BPA was found in 72% of samples analyzed and its concentration levels fluctuated from 3.6 to 52.9 ng/g (median 17.7 ng/g). The BPS concentration levels were higher - from 13.4 to 1054.9 ng/g (median 98.7 ng/g). We also found that gender, age, and the presence of artificial hair color (hair dye) did not affect the BPA and BPS levels in the hair. CONCLUSIONS This study has shown that hair samples may be used to measure the levels of bisphenols, and that exposure to BPS may be greater than that to BPA in this area. The investigation also revealed that hair analysis is a useful approach for the biomonitoring of BPA and BPS levels in human organisms.

Hair Sample Analysis as a Method of Monitoring Exposure to Bisphenol A in Dogs.

Bisphenol A (BPA) is an organic substance widely used in the plastics industry. It penetrates food and environment and, as an endocrine disruptor, has detrimental effects on human organisms. Pet animals, which live in the immediate vicinity of humans, are also exposed to BPA; however, knowledge regarding the exposure of dogs to this substance is extremely scarce. This is the first study in which hair analysis has been used to biomonitor BPA in 30 dogs using liquid chromatography and tandem mass spectrometry techniques. The presence of BPA in concentration levels above the method detection limit (1.25 ng/g) was noted in 93.33% of samples. BPA concentration levels were found to range from 7.05 ng/g to 436 ng/g (mean 81.30 ng/g). Statistically significant differences in BPA concentration levels were found between animals with physiological weight and animals with abnormal weight (skinny and obese). In turn, differences between males and females, as well as between young, middle-aged and old dogs, were not statistically significant. The obtained results have clearly shown that hair analysis is a useful method to evaluate the exposure of dogs to BPA. This study also confirmed that dogs are exposed to BPA to a large extent, and this substance may play a role as a pathological factor in this animal species. However, many aspects connected to the influence of BPA on canine health status are unclear and need further study.

The Presence of Triclosan in Human Hair Samples in Poland-A Pilot Study.

Triclosan (TCS) is an organic substance showing antibacterial action, which is commonly used in many branches of industry, including, among others, cosmetics, pharmaceuticals and the food industry. TCS may penetrate into living organisms and negatively affect the health of humans and animals. The majority of previous investigations on TCS biomonitoring in humans have been performed on urine, but currently, studies on hair samples are becoming increasingly important. The aim of this study was to evaluate TCS concentration levels in residents of Olsztyn, a city in northeastern Poland, using a liquid chromatography-mass spectrometry technique. The presence of TCS was observed in 96.7% of samples tested, with concentration levels from 37.9 pg/mg to 3386.5 pg/mg. The mean concentration level of TCS in the present study was 402.6 (±803.6) pg/mg, and the median value was 103.3 pg/mg. Although there were some differences in TCS concentration levels between males and females, humans of various ages and humans with colored and natural hair had no statistically significant differences in TCS concentration levels. The obtained results have clearly indicated that people living in northeastern Poland are exposed to TCS to a large degree, and hair analysis, despite some limitations, is a suitable method for TCS biomonitoring in humans.

Concentrations of bisphenol a (BPA) in fresh pork loin meat under standard stock-farming conditions and after oral exposure - A preliminary study.

Bisphenol A (BPA) is a substance commonly used in the production of plastics. It may be leached from plastics, penetrate to food and has multidirectional negative effects on living organisms. The aim of this study was to evaluate BPA levels in fresh pork meat collected immediately after the death of animals kept in standard stock-farming conditions, as well as from animals receiving various oral doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b. w./day). In animals kept in standard conditions, the average concentration of BPA in loin meat amounted to 37.03 ± 6.18 ng/g dry weight (d.w.). In animals receiving lower and higher doses of BPA, this value achieved 47.44 ± 4.39 ng/g d. w. and 214.30 ± 66.73 ng/g d. w, respectively. The results show that pork meat may be a source of BPA in human food and the presence of BPA in the meat may result from the exposure of animals over their lifetime. This observation shows that the elimination of BPA from the production of items used for animal husbandry and animal feed may reduce meat contaminated with this substance and, therefore, increase consumer safety.

The use of Savary-Gilliard dilators in the treatment of an oesophageal stricture in a cat.

Oesophageal strictures in cats and dogs are relatively rare and the cause of this disorder can be multifactorial. However, the most common cause in cats is an inflammatory process.Conservative treatment strategies for this disorder includes image-guided interventions. Endoscopic methods are a form of a minimally invasive surgical treatment of the oesophageal strictures. Several endoscopic methods for the therapy of this condition are known, one of them is Savary-Gilliard dilators technique.In the present study of a case of oesophageal stricture in a cat, caused probably by doxycycline treatment without water administration, the authors used the Savary-Gilliard dilators as a therapy for its condition. The animal underwent 3 endoscopy procedures, where in the third one no abnormality in the oesophagus was observed. Moreover, the cat was asymptomatic 6 months after the last oesophagoscopy.In the authors opinion, based on the present case, some experience of the authors and previously described studies, the Savary-Gilliard dilators seems to be a safe, effective, relatively cheap and minimally invasive method of the oesophageal stricture therapy in the cat.

Biomonitoring parabens in dogs using fur sample analysis - Preliminary studies.

Parabens are widely used in the food, cosmetics and pharmaceutical industry and are widespread in the environment. As endocrine disruptors, parabens have adverse effects on living organisms. However, knowledge of the exposure of domestic animals to parabens is extremely scarce. Therefore, this study assessed the exposure level of dogs to three parabens commonly used in industry (i.e. methylparaben - MeP, ethylparaben - EtP and propylparaben - PrP) using fur sample analysis in liquid chromatography-tandem mass spectrometry. The presence of parabens has been noted in the samples collected from all dogs included in the study (n = 30). Mean concentrations of MeP, EtP and PrP in the fur of dogs were 176 (relative standard deviation - RSD = 127.48%) ng/g dry weight (dw), 48.4 (RSD = 163.64%) ng/g dw and 79.8 ng/g dw (RSD = 151.89%), respectively. The highest concentrations were found for MeP (up to 1023 ng/g dw). Concentrations of MeP and EtP in males were statistically higher than those in females (p < 0.05). Statistically significantly higher concentration levels of PrP in young animals (up to three years old) were also found. This is the first study concerning the use of fur samples to evaluate the exposure of domestic animals to parabens. The results indicate that an analysis of the fur may be a useful tool of paraben biomonitoring in dogs. The presence of parabens in the canine fur also suggests that these substances may play a role in veterinary toxicology. However, many aspects connected with this issue are not clear and require further study.

The Comparison of the Influence of Bisphenol A (BPA) and Its Analogue Bisphenol S (BPS) on the Enteric Nervous System of the Distal Colon in Mice.

Bisphenol A (BPA), commonly used as a plasticizer in various branches of industry has a strong negative effect on living organisms. Therefore, more and more often it is replaced in production of plastics by other substances. One of them is bisphenol S (BPS). This study for the first time compares the impact of BPA and BPS on the enteric neurons using double immunofluorescence technique. It has been shown that both BPA and BPS affect the number of enteric neurons containing substance P (SP), galanin (GAL), vasoactive intestinal polypeptide (VIP), neuronal isoform of nitric oxide synthase (nNOS-a marker of nitrergic neurons) and/or vesicular acetylcholine transporter (VAChT- a marker of cholinergic neurons). The changes noted under the impact of both bisphenols are similar and consisted of an increase in the number of enteric neurons immunoreactive to all neuronal factors studied. The impact of BPS on some populations of neurons was stronger than that noted under the influence of BPA. The obtained results clearly show that BPS (similarly to BPA) administered for long time is not neutral for the enteric neurons even in relatively low doses and may be more potent than BPA for certain neuronal populations.

Evaluation of human exposure to parabens in north eastern Poland through hair sample analysis.

Parabens (PBs) are a group of substances commonly used in industry. They also pollute the environment, penetrate into living organisms and adversely affect various internal organs. During this study, the degree of exposure of people living in Olsztyn, a city in north eastern Poland, to selected parabens most often used in industry was studied. The chemicals under investigation included: methyl paraben-MePB, ethyl paraben-EtPB, propyl paraben-PrPB, benzyl paraben BePB and butyl paraben -BuPB. To this aim, hair samples collected from the scalps of 30 volunteers were analyzed using a liquid chromatography-mass spectrometry technique. All PBs studied were present in a high percentage of analyzed samples (from 76.7% in the case of BePB to 100% in the case of MePB and PrPB). The mean concentration levels were 4425.3 pg/mg for MeBP, 704.0 pg/mg for EtPB, 825.7 pg/mg for PrPB, 135.2 pg/mg for BePB and 154.5 pg/mg for BuPB. Significant differences in PB concentration levels between particular persons were visible. On the other hand, gender, age and artificial hair coloring did not cause statistically significant differences in PB levels. Obtained results have clearly indicated that people living in north eastern Poland are exposed to various PBs, and therefore these substances may affect their health status. However, the evaluation of PBs influence on human health requires further research.

The Influence of Bisphenol A (BPA) on the Occurrence of Selected Active Substances in Neuregulin 1 (NRG1)-Positive Enteric Neurons in the Porcine Large Intestine.

Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances.

Bisphenol A affects vipergic nervous structures in the porcine urinary bladder trigone.

Bisphenol A (BPA) is used in the production of plastics approved for contact with feed and food. Upon entering living organisms, BPA, as a potent endocrine disruptor, negatively affects various internal organs and regulatory systems, especially in young individuals. Although previous studies have described the neurotoxic effects of BPA on various tissues, it should be underlined that the putative influence of this substance on the chemical architecture of the urinary bladder intrinsic innervation has not yet been studied. One of the most important neuronal substances involved in the regulation of urinary bladder functions is vasoactive intestinal polypeptide (VIP), which primarily participates in the regulation of muscular activity and blood flow. Therefore, this study aimed to determine the influence of various doses of BPA on the distribution pattern of VIP-positive neural structures located in the wall of the porcine urinary bladder trigone using the double-immunofluorescence method. The obtained results show that BPA influence leads to an increase in the number of both neurons and nerve fibres containing VIP in the porcine urinary bladder trigone. This may indicate that VIP participates in adaptive processes of the urinary bladder evoked by BPA.

Assessment of exposure to perfluoroalkyl substances (PFASs) in dogs by fur analysis.

Poly- and perfluoroalkyl substances (PFASs) are a large group of chemicals commonly used in various branches of industry, which may adversely affect the living organisms. The aim of this study were to evaluate exposure of dogs to six selected PFASs: five perfluoroalkyl carboxylic acids (perfluorobutanoic acid - PFBuA, perfluoropentanoic acid - PFPeA, perfluorohexanoic acid - PFHxA, perfluoroheptanoic acid - PFHpA, perfluorooctanoic acid - PFOA) and perfluorooctane sulfonic acid (PFOS) through the analysis of fur samples. To our knowledge this is the first study concerning the use of fur samples to evaluation of exposure of domestic animals to PFASs. Relationship between PFASs concentration and age, gender and body weight of animals was also evaluated. Fur samples were collected from 30 dogs living in Olsztyn (Poland). All PFASs studied were detected in the canine fur samples. The highest concentrations were observed in the case of PFOA and PFBuA, detected at concentrations in the range between 1.51 and 66.7 ng/g and 0.98-26.6 ng/g, respectively. During the present study generally no statistically significant differences dependent on gender, age and body weight of animals were found. This study confirms the suitability of fur samples for biomonitoring of exposure to PFASs in domestic animals, what may be important in veterinary toxicology.