Search

Milk has been suggested to be a possible source of oestrogenically active compounds. In order to assess the health risk for milk consumers and ensure the safety of this staple part of the human diet, it is important to study the effect of xenooestrogen mixtures present in milk. This investigation used the available in vivo model to learn to what extent such compounds may be endocrine disruptors.

Introduction: Albendazole is used to treat endoparasitic diseases in animals and humans. After oral administration, it is quickly oxidised into its pharmacologically active metabolite albendazole sulfoxide and then to sulfone. However, it is not clear which compound is responsible for toxic effects towards mammalian cells. Material and Methods: The model systems comprised cultures of isolated rat hepatocytes, two hepatoma cell lines (FaO, HepG2), and non-hepatic Balb/c 3T3 line. Cells were exposed for 24, 48, and 72 h to eight concentrations of albendazole ranging from 0.05 to 100 μg/mL. At all three time points cytotoxic effects were assessed by MTT assay and metabolites in the culture media were determined by LC-MS/MS analysis. Results: The effective concentrations EC50-72h showed that Balb/c 3T3 cells were the most sensitive to albendazole (0.2 ±0.1 μg/mL) followed by FaO (1.0 ±0.4 μg/mL), and HepG2 (6.4 ±0.1 μg/mL). In the case of isolated hepatocytes this value could not be attained up to the highest concentration used. Chemical analysis revealed that the concentrations of albendazole in hepatocytes and HepG2 and FaO culture media gradually decreased with incubation time, while the concentrations of its metabolites increased. The metabolism in isolated hepatocytes was dozens of times greater than in HepG2 and FaO cells. Two metabolites (albendazole sulfoxide, albendazole sulfone) were detected in isolated hepatocytes and HepG2 culture medium, one (albendazole sulfoxide) in FaO culture medium and none in Balb/c 3T3. Conclusion: The obtained data indicate that metabolism of albendazole leads to its detoxification. The lower cytotoxic potential of metabolites was confirmed in the independent experiments in this study.

Introduction: The cytotoxicity of anthelmintic agent, albendazole (ABZ) and its two major metabolites, sulfoxide (ABZSO) and sulfone (ABZ-SO2), on non-hepatic Balb/c 3T3 line, two hepatoma cell lines (FaO, HepG2), and isolated rat hepatocytes was investigated. Material and Methods: Cell cultures were exposed for 24, 48, and 72 h to eight concentrations of the compounds ranging from 0.05 to 100 μg/mL (ABZ) and from 0.78 to 100 μg/mL (ABZ-SO and ABZ-SO2). Three different assays were applied in which various biochemical endpoints were assessed: lysosomal activity - neutral red uptake (NRU) assay, proliferation - total protein contents (TPC) assay and lactate dehydrogenase (LDH) leakage assay. Results: The most toxic was albendazole whose EC50 values calculated from the concentration effect curves ranged from 0.2 to 0.5 μg/mL (Balb/c 3T3 ) and from 0.4 to 73.3 μg/mL (HepG2). Rat hepatoma line and isolated rat hepatocytes were less sensitive to the impact of ABZ. Toxic action expressed as EC50 was recorded after 72 h exposure only in LDH release assay at 0.8 μg/mL and 9.7 μg/mL respectively. The toxicity of metabolites was much lower. The most sensitive to ABZ-SO were fibroblasts and EC50-72h values were similar in all three assays used, i.e. NRU (14.1 μg/mL), TPC (15.8 μg/mL), and LDH (20.9 μg/mL). In the case of ABZ-SO2 the mean effective concentrations were the highest, and could be reached only in one LDH assay. These values (μg/mL) were as follows: 65.3 (FaO), 65.4 (HepG2), 75.8 (hepatocytes), and 77.4 (Balb/c 3T3). Conclusion: The differences in in vitro toxicity of albendazole depend on metabolic ability of the cellular models. Primary cultured rat hepatocytes represent a valuable tool to study the impact of biotransformation on the cytotoxicity of drugs.

Fungi such as Aspergillus spp. and Fusarium spp., which are commonly found in the environment, pose a serious global health problem. This study aims to present the results of epidemiological studies, including clinical cases, on the relationship between human exposure to some mycotoxins, especially zearalenone and aflatoxin, and the occurrence of reproductive disorders. In addition, examples of methods to reduce human exposure to mycotoxins are presented. In March 2023, various databases (PubMed, Google Scholar, EMBASE and Web of Science) were systematically searched using Google Chrome to identify studies evaluating the association between exposure to mycotoxins and the occurrence of complications related to impaired fertility or cancer incidence. The analysed data indicate that exposure to the evaluated mycotoxins is widespread and correlates strongly with precocious puberty, reduced fertility and increased cancer incidence in women and men worldwide. There is evidence to suggest that exposure to the Aspergillus mycotoxin aflatoxin (AF) during pregnancy can impair intrauterine foetal growth, promote neonatal jaundice and cause perinatal death and preterm birth. In contrast, exposure to the Fusarium mycotoxin zearalenone (ZEA) leads to precocious sexual development, infertility, the development of malformations and the development of breast cancer. Unfortunately, the development of methods (biological, chemical or physical) to completely eliminate exposure to mycotoxins has limited practical application. The threat to human health from mycotoxins is real and further research is needed to improve our knowledge and specific public health interventions. [ABSTRACT FROM AUTHOR]

Copyright of Zycie Weterynaryjne is the property of Polish National Veterinary Chamber and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: A series of thiazolo[4,5-b]pyridin-2(3H)-one derivatives were obtained via [3 + 3]-cyclization of 4-amino-5H-thiazol-2-one and α,β-unsaturated ketones or α-ketoacids. The structures of newly synthesized compounds were established by spectral data and a single-crystal X-ray diffraction analysis. Target compounds were screened for their anticancer activity according to US NCI protocols and moderate inhibitory activity against the tested cell line was confirmed. 5-Phenyl-7-(pyridin-3-yl)-3H-thiazolo[4,5-b]pyridin-2-one (3) and 2-oxo-7-thiophen-2-yl-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid (12) were screened for their cytotoxicity effects on HepG2 and Balb/c 3T3 cells which revealed promising results using MTT, NRU and TPC assays.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Copyright of Environmental Medicine / Medycyna Środowiskowa is the property of Witold Chodzki Institute of Rural Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: The use of cell cultures can be an important alternative for animal experiments. Therefore, it seems reasonable to use in vitro models to compare the liver metabolism of a drug in different animal species. Chloramphenicol is an effective broad-spectrum antibiotic used in human and pets. The toxicity of chloramphenicol is complex and differs among animal species mainly depending on the biotransformation. The purpose of this study was to assess chloramphenicol metabolism on its cytotoxicity in primary turkey and rat hepatocyte cultures, also in human hepatoma (HepG2) cells and nonhepatic, Balb/c 3T3 fibroblasts. To the best of our knowledge, this is the first report of differences in chloramphenicol metabolism in primary turkey and rat hepatocyte cultures. The two metabolites of the drug were detected in turkey and rat hepatocyte cultures. The amount of one metabolite of chloramphenicol was closely related to the cytotoxicity of the drug. The primary turkey and rat hepatocyte cultures were more sensitive to chloramphenicol than HepG2 cells and Balb/c 3T3 fibroblasts. The primary hepatocyte cultures represent valuable tools with which to study the biotransformation of xenobiotics and determine species differences in their metabolism and toxicity. The purpose of this study was to assess the formation of chloramphenicol metabolites in primary turkey and rat hepatocyte cultures and human hepatoma (HepG2) cells and nonhepatic, Balb/c 3T3 fibroblasts. Additionally, the cytotoxicity of the drug was assessed through three biochemical endpoints: mitochondrial and lysosomal activity and cellular membrane integrity after 24 and 48 h exposure. The two metabolites of the drug, chloramphenicol glucuronide and nitroso-chloramphenicol, were detected to the greatest extent in both primary hepatocyte cultures by liquid chromatography–tandem mass spectrometry. Toxic nitroso-chloramphenicol was the main metabolite in the primary turkey hepatocyte cultures, but it was not in the primary rat hepatocyte cultures. The most affected endpoint in turkey and rat hepatocyte cultures was the disintegration of the cellular membrane, but in the cell lines, mitochondrial and lysosomal activities underwent the greatest change. The primary hepatocyte cultures represent valuable tools with which to study the species differences in the biotransformation and toxicity of drugs. To the best of our knowledge, this is the first report of differences in chloramphenicol metabolism in primary turkey and rat hepatocyte cultures. [ABSTRACT FROM AUTHOR]

Background: The risk for public health posed by endocrine disruptors present in food is relatively new issue. Our current understanding of human exposure is mainly based on the residue analysis of selected compounds. With such approach potential, effects of mixtures, including so-far unidentified compounds are not taken into consideration. Therefore, the knowledge of overall hormonal activity in food samples is of big importance., Objective: Milk and dairy products are a rich source of estrogens but very rarely undergo testing for estrogenic activity. For this reason the rodent uterotrophic bioassay is one of the most useful tool. This preliminary study was conducted in immature hamsters to assess commercially available milk. The endpoint measured was uterine weight increase., Material and Methods: Fifteen-day old females received ad libitum throughout 7 days commercially available milk i.e. raw goat’s, raw cow’s, processed 3.2% UHT, and for comparison soy milk. The animals of negative control group received water but positive control group got 17β - estradiol (E2) at the concentration of 100 ng/ml., Results: All samples of milk showed estrogenic activity as follow: goat’s >cow’s >soy >processed milk. Significant increase of uteri weights were recorded in goat’s (p<0.001) and cow’s milk (p<0.01). However, the activity was approximately 5-fold lower than induced by 17β-estradiol. The ratio uterine weight/body weight (%) in negative control was 0.096%, in milk experimental groups ranged from 0.112% to 0.153% and in positive control this value was 0.493%., Conclusion: The results suggest that commercially available milk has a weak uterotrophic activity. Further in vivo and in vitro studies are warranted to gain more insight into the estrogenic risk from milk and other dairy products.