The growing use of cytostatic drugs is gaining relevance as an environmental concern. Environmental and distribution studies are increasing due to the development of accurate analytical methods, whereas ecotoxicological studies are still lacking. The aim of the present study was to investigate the acute and chronic toxicity of six cytostatics (5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib) belonging to five classes of Anatomical Therapeutic Classification (ATC) on primary consumers of the aquatic chain (Daphnia magna, Ceriodaphnia dubia, Brachionus calyciflorus, and Thamnocephalus platyurus). Acute ecotoxicological effects occurred at concentrations in the order of mgL(-)(1), higher than those predicted in the environment, and the most acutely toxic drugs among those tested were cisplatin and doxorubicin for most aquatic organisms. For chronic toxicity, cisplatin and 5-fluorouracil showed the highest toxic potential in all test organisms, inducing 50% reproduction inhibition in crustaceans at concentrations on the order of μgL(-)(1). Rotifers were less susceptible to these pharmaceuticals. On the basis of chronic results, the low effective concentrations suggest a potential environmental risk of cytostatics. Thus, this study could be an important starting point for establishing the real environmental impact of these substances.
The eco-genotoxicity of six anti-neoplastic drugs, 5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib, belonging to five classes of anatomical therapeutic classification (ATC), was studied applying the in vivo comet assay on cells from whole organisms of Daphnia magna and Ceriodaphnia dubia. For the first time, this test was performed in C. dubia. In addition, to have a wider genotoxic/mutagenic profile of the anticancer drugs selected, SOS chromotest and Salmonella mutagenicity assay were performed. The comet results showed that all drugs induced DNA damage, in both Cladocerans, with environmental concern; indeed Doxorubicin induced DNA damage in the order of tens of ng L(-1) in both crustaceans, as well as 5-flurouracil in C. dubia and cisplatin in D. magna. In the SOS Chromotest all drugs, except imatinib, were able to activate the repair system in Escherichia coli PQ37 while in the Salmonella mutagenicity assay, doxorubicin was the only drug able to cause direct and indirect frameshift and base-pair substitution mutations. Comet assay was the most sensitive tool of genotoxic exposure assessment, able to detect in vivo the adverse effects at concentration lower than those evaluated in vitro by bacterial assays.
The antioxidant properties of nine different samples of freshly drawn, pasteurised and UHT milk were examined before and after fermentation with several lactobacilli, individually and in combination with the yeast Saccharomyces boulardii. The results showed no statistical differences for the content in proteins, fats and carbohydrates of the different milk. The antioxidant properties of the unfermented milk were positively affected by the thermal treatment. All samples of fermented milk had a greater antioxidant activity than unfermented but only for the freshly drawn milk that increase was significantly different. The co-incubation of lactobacilli with the yeast determined a stronger antioxidant activity especially for the freshly drawn milk. The stability of the tested strains during storage in standard conditions was determined in UHT fermented milk to enable a possible use in probiotic food production. The results showed that the yeast incubated with lactobacilli determined an improvement of the viability of bacteria.Antioxidant properties of milk fermented with LAB and yeast A. Parrella et al.
Anticancer drugs, interfering with DNA in every living organism, may pose a threat to aquatic environment, even more when they occur as complex mixtures. We investigated the combined long term toxic potential of four anti-neoplastic drugs (5-fluorouracil [5-FU], cisplatin [CDDP], etoposide [ET] and imatinib mesylate [IM]) testing their binary mixtures on two primary consumers of the freshwater aquatic chain with close phylogenetic relationship: Daphnia magna and Ceriodaphnia dubia. The combined toxicities were assessed using two distinct effect sizes that should be observed if Bliss independence holds. Direct statistical comparison by analysis of variance of single and combined toxicities under the assumption of Bliss independence allowed to accept or reject the independency hypothesis. Independency was confirmed for all mixtures both in D. magna and in C. dubia, except for IM+ ET and IM+CDDP in D. magna and for ET+CDDP and ET+5-FU in C. dubia which at the highest concentrations showed an antagonistic interaction. A synergic tendency was found testing IM+CDDP on C. dubia at the lowest concentration selected. Thus, the chronic ecotoxicological data evaluated in this study show not only a potential environmental risk of anticancer drugs, especially considering their potential synergistic effects, but also the necessity to integrate statistical models with experimental data to establish the real environmental impact of such compounds.
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