Lead, cadmium, and other trace elements in the liver of golden eagles and white-tailed eagles: recent data from Poland and a systematic review of previous studies.

The golden eagle (Aquila chrysaetos) and the white-tailed eagle (Haliaeetus albicilla), being apex predators and facultative scavengers, can bioaccumulate different environmental contaminants, including toxic elements that may adversely affect their health. We analyzed the levels of cadmium (Cd), lead (Pb), and other metals and metalloids, including arsenic (As), barium (Ba), beryllium (Be), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), selenium (Se), thorium (Th), thallium (Tl), uranium (U), vanadium (V), and zinc (Zn) in liver samples taken from three golden eagles and 36 white-tailed eagles that were found dead across Poland to verify their exposure. We also used a systematic review to summarize the available literature data on Cd, Pb, and other studied elements in the liver of both eagle species. Analyses of trace elements in the liver samples of the Polish eagles revealed interspecific differences in Cd, Cu, and Mn and differences in Co, Mn, Tl, and Zn among study regions. All elements tested except Pb were below the suggested thresholds linked with adverse health effects in birds. The hepatic Pb found in almost half of all the tested individuals suggests environmental exposure to this toxic element. One of the tested white-tailed eagles had hepatic Pb above the threshold of sublethal poisoning. Although our results seem optimistic, as previous Polish studies showed a higher prevalence of birds with hepatic Pb exceeding the toxicity threshold, they indicate that exposure to this toxic metal could still pose an additional threat to the health of Polish eagles.

Identification of metabolites of anticancer candidate salinomycin using liquid chromatography coupled with quadrupole time-of-flight and hybrid triple quadrupole linear ion trap mass spectrometry.

RATIONALE: Salinomycin is an ionophore antibiotic with potential anticancer activity. The history of its use in veterinary medicine shows large differences in species susceptibility to its toxicity. At the same time, the results of research to date suggest a correlation between the extent and pathways of ionophore biotransformation and its toxicity. The biotransformation pattern of salinomycin has not been studied so far. METHODS: Extracts from culture media of human hepatoma cells (HepG2) exposed to salinomycin were analysed with two mass spectrometry techniques. For the first one, micro-liquid chromatography coupled with a quadrupole time-of-flight (Q-TOF) mass spectrometer was used. In the second approach, high-performance liquid chromatography was coupled with a hybrid triple quadrupole linear ion trap. Both experiments were operated in positive electrospray ionization mode. To identify unknown salinomycin metabolites, information-dependent acquisition was applied. RESULTS: Metabolites identified with tandem mass spectrometry included hydroxylated, demethylated and hydroxylated-demethylated derivatives, in total 14 compounds. Using high resolution, only eight isomers of hydroxysalinomycin were detected. The efficiency of biotransformation was low, and so was the abundance of the signals; only for two metabolites did the signal exceed 1% of the salinomycin signal. The analysis of fragmentation patterns narrowed the structure combinations but the actual modification site could not be specified. CONCLUSIONS: Tandem mass spectrometry was more sensitive in the identification of salinomycin metabolites in comparison to the Q-TOF approach. Because of low efficiency of biotransformation of the applied model, the obtained fragmentation data are not sufficient to fully characterize the detected compounds. A study with more metabolically active primary hepatocytes is needed.

Absence of evidence or evidence of absence? A transfer and depletion study of Sudan I in eggs.

Sudan I is a carcinogenic industrial azo-dye, forbidden for use in food. However, it has been detected in food on several occasions, such as in paprika, used in animal husbandry to enhance egg yolk colour. Therefore, an animal experiment was designed to simulate the transfer of Sudan I to eggs after its unintentional administration to laying hens. A group of laying hens (n=18) received feed contaminated with Sudan I at the raising concentrations: 0.45mg/kg, 4.97mg/kg and 42.1mg/kg. Residues of Sudan I were detected in egg yolks (0.29±0.03µg/kg, mean±SD) only after the administration of the feed contaminated with the dye at the highest concentration. The determined concentrations were much lower than expected based on the compound's lipophilicity. In conclusion, the transfer of Sudan I to eggs was limited and strongly dependent on its concentration in feed.

Nonsteroidal mycotoxin alternariol is a full androgen agonist in the yeast reporter androgen bioassay.

Alternariol (AOH) is a toxic metabolite of phytopathogenic fungi of the Alternaria spp. and important contaminant of agricultural commodities. According to the recent studies, AOH has a potential to modulate the endocrine system of humans and animals. In the view of these reports, our study addressed the effects of AOH on human estrogen receptor (hERα) and androgen receptor (hAR) signaling with the use of the yeast estrogen and androgen reporter bioassays. Our results show that, apart from a weak estrogenic response, AOH induces full androgenic response of the bioassay with the EC50 of 269.4µM. The androgenic potency of AOH relative to testosterone (T) is 0.046%. Moreover, in the presence of T, AOH at 5µM acts as a weak antiandrogen, whereas at higher concentrations AOH sum up with the androgenic activity of T in a dose-dependent manner, suggesting additive effect. To our knowledge it is the first report of the androgenic potency of natural, nonsteroidal substance and may have the impact on the direction of the further studies. Further research is warranted to clarify the role of AOH in disruption of AR signaling in humans and animals.

Comparison of Albendazole Cytotoxicity in Terms of Metabolite Formation in Four Model Systems.

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.