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Levels and risks of surface contamination by thirteen antineoplastic drugs in the Czech and Slovak hospitals and pharmacies [Erratum: April 2022, v.29(18); p.26820]
2022
Doležalová, Lenka | Bláhová, Lucie | Kuta, Jan | Hojdarová, Tereza | Kozáková, Šárka | Bláha, Luděk
The consumption of hazardous antineoplastic drugs (ADs) used in anticancer chemotherapies is steadily increasing representing thus risks to both human health and the environment. Hospitals may serve as a contamination source, and pharmacists preparing the antineoplastic drugs (ADs) as well as nurses administering chemotherapy and caring for oncology patients are among the healthcare professionals being highly exposed. Here, we present the results of systematic monitoring (2018–2020) of surface contamination by 13 ADs in the pharmacies and hospitals in the Czech Republic (CZ; large-scale monitoring, 20 workplaces) and Slovak Republic (SK; pilot study at 4 workplaces). The study evaluated contamination by three commonly monitored ADs, i.e., 5-fluorouracil (FU), cyclophosphamide (CP), and platinum (total Pt representing cis-, carbo-, and oxaliplatin) together with ten less explored ADs, i.e., gemcitabine (GEM), ifosfamide (IF), paclitaxel (PX), irinotecan (IRI), docetaxel (DOC), methotrexate (MET), etoposide (ETOP), capecitabine (CAP), imatinib (IMAT), and doxorubicin (DOX). Floors and desktop surfaces in hospitals (chemotherapy application rooms, nurse working areas) were found to be more contaminated, namely with CP and Pt, in both countries when compared to pharmacies. Comparison between the countries showed that hospital surfaces in SK are generally more contaminated (e.g., CP median was 20 times higher in SK), while some pharmacy areas in the CZ were more contamined in comparison with SK. The newly studied ADs were detected at lower concentrations in comparison to FU, CP, and Pt, but some markers (GEM, IF, PX, and IRI) were frequently observed, and adding these compounds to routine monitoring is recommended.
Show more [+] Less [-]Antioxidant, anti-inflammatory, and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats
2021
Abdulkareem Aljumaily, Sara Asaad | Demir, Mehmet | Elbe, Hulya | Yigitturk, Gurkan | Bicer, Yasemin | Altinoz, Eyup
Doxorubicin (DOX) is a well-known chemotherapeutic drug for most malignancies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. In the present study, we aimed to investigate the effects of crocin on doxorubicin-induced cardiotoxicity in rats. Forty rats were randomly divided into four groups: (a) control [received normal saline as a dose of 1 ml/kg by intraperitoneal injection (ip) for 15 days], (b) crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX+crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection, and crocin as a dose of 40 mg/kg/24h i.p for 15 days). As compared to the controls, the results showed that DOX administration caused significant increases in lipid indices [triglyseride (TG), low-dencity lipoproteins (LDL) (p<0.001), and very low-dencity lipoproteins (VLDL) (p<0.005)], oxidative stress parameters [malondialdehyde (MDA) and total oxidant status (TOS) (p<0.001)] and cardiac markers [creatine kinase-muscle/brain (CK-MB) and cardiac troponin I (cTnI) (p<0.001)]. Besides, significant decreases in antioxidant defense systems [glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) (p<0.001)] were observed. The present study also demonstrated that co-administration of crocin with DOX significantly ameliorated the lipid profile (p<0.005), cardiac markers (p<0.005), and oxidative stress indices (p<0.001) as compared to DOX group. Histopathologically, significant increase in the mean histopathological damage score (MHDS) was found in the DOX group as compared to the controls (p<0.001). In contrast, the administration of crocin with DOX alleviated MHDS in myocardium (p<0.001). Taken together, our results reveal that crocin might be a cardioprotective agent in DOX-treated patients for cancer.
Show more [+] Less [-]Occurrence and Ecotoxicological Risk Assessment of 14 Cytostatic Drugs in Wastewater
2014
Martin, Julia | Camacho-Muñoz, Dolores | Santos, Juan Luis | Aparicio, Irene | Alonso, Esteban
Cytostatic drugs are pharmaceutically active compounds used in chemotherapy to prevent or disrupt cell division. Only a few environmental studies have been focused on cytostatic drugs, in spite of their toxicity, their increasing consumption, and their discharge into municipal sewage. This fact can be mainly due to the lack of methods for their simultaneous analysis. This research describes the occurrence of 14 cytostatic drugs in influent and effluent wastewater from four wastewater treatment plants located in Seville (Spain) during 1-year period. A preliminary environmental risk assessment was also carried out. Five cytostatic drugs (cytarabine, etoposide, gemcitabine, iphosphamide, and methotrexate) were detected in influent wastewater at concentration levels up to 464 ng L⁻¹(cytarabine). Six of them (cytarabine, doxorubicin, gemcitabine, iphosphamide, paclitaxel, and vinorelbine) were detected in effluent wastewater at concentration levels up to 190 ng L⁻¹(cytarabine). Most of the detected cytostatic drugs are not significantly removed during wastewater treatment. Nevertheless, neither ecotoxicological nor genotoxical risks are expected to occur at the measured concentrations on the aquatic environment.
Show more [+] Less [-]Doxorubicin, L-arginine, or their combination as a prophylactic agent against hepatic carcinoma in mice
2021
Al-Shahari, Eman A. | El Barky, Amira Ragab | Mohamed, Tarek M. | Alm-Eldeen, Abeer A.
Hepatocellular carcinoma (HCC) is one of the ten most commonly diagnosed cancers. Doxorubicin is an antibiotic used in cancer treatment protocols that has several side effects. L-Arginine is a non-essential amino acid that is used as immune system activation and antitumor drugs. Therefore, the current study was designed to compare using doxorubicin, L-arginine, or their combination as a prophylactic agent against hepatic carcinoma induced by hepatocellular carcinoma cells (HepG2) injection in mice. The mice were divided into five groups: normal mice and mice that received HepG2, doxorubicin and HepG2, L-arginine and HepG2, and doxorubicin, L-Arginine, and HepG2, respectively. Liver function test as, aspartate transaminase (AST) and alanine transaminase (ALT), and alpha-fetoprotein (AFP), caspase 3, interleukin 6 (IL-6), tumor necrotic factor (TNF), lipid peroxidation (NDA), and some antioxidant parameters were determined. A significant increase in AST and ALT, α-fetoprotein, TNF-α, and cytokines IL6 and MDA and a significant decrease in the serum caspase and liver catalase were determined in HepG2-injected mice. Moreover, some large hyperchromatic heptocytes were observed and the percentage of the positive area/field of HepPar-1, the most specific HCC marker, was 9.56%. Interestingly, mice that received doxorubicin, L-arginine, or their combination showed an improvement in some of the previous parameters. The improvement was more prominent with L-arginine administration.
Show more [+] Less [-]Cytogenotoxic Effects of Spent Pot Liner (SPL) and Its Main Components on Human Leukocytes and Meristematic Cells of Allium cepa
2016
Palmieri, Marcel José | Andrade-Vieira, Larissa Fonseca | Trento, Marcus Vinícius Cardoso | de Faria Eleutério, Mateus William | Luber, Jaquelini | Davide, Lisete Chamma | Marcussi, Silvana
The Spent Pot Liner (SPL) is a toxic solid waste from the aluminum industry. The genotoxic potential of SPL and its main chemical components (fluoride, cyanide, and aluminum) were evaluated on vegetal (Allium cepa L. system test) and human cells (comet assay) in the present study. Meristematic cells from A. cepa submitted to the treatments presented a reduction in the mitotic index (MI) and an increase in the frequency of chromosome alterations (CA). The SPL treatment reduced MI in 50 % when compared to the negative control. In addition, there were significant reductions in MI on the cyanide and aluminum treatments. All frequencies of chromosome alterations observed to the treatments were statistically different from control, and cyanide was the most cytogenotoxic component. The exposed cells to the treatments also increased the frequency of condensed nuclei. The comet assay on human leukocytes demonstrated that all treatments induced DNA fragmentation. Fluoride and SPL showed similar damages to the positive control (doxorubicin, UA = 259.7) and higher than the negative control (CaCl₂ 0.01 M, UA = 16.5). The aluminum induced intermediary damage, and the cyanide was responsible for minor damage. In conclusion, both SPL and its main components presented genotoxic and mutagenic potential on evaluated cells. Fluoride was the main genotoxic component for human leukocytes while cyanide leads the higher alterations for A. cepa meristematic cells. Thus, the storage and discard of this residue should be regulated and supervised more closely in order to reduce the risk of environmental pollution and its contact with human.
Show more [+] Less [-]Magnetite graphene oxide modified with β-cyclodextrin as an effective adsorbent for the removal of methotrexate and doxorubicin hydrochloride from water
2022
Ghafoori, Mohammad | Cheraghi, Mehrdad | Sadr, Maryam Kiani | Lorestani, Bahareh | Sobhanardakani, Soheil
The purpose of this investigation was to analyze the performance of magnetite graphene oxide modified with β-cyclodextrin (GO@Fe₃O₄@β-CD) for adsorption of methotrexate (MTX) and doxorubicin (DOX) from aqueous solutions. Characterization of GO@Fe₃O₄@β-CD was carried out using some methods. The perfect conditions for the adsorption of MTX and DOX were 7.0, 45 min, 20 mg, and 25 °C for solution pH, contact time, adsorbent dose, and temperature, respectively, with removal efficiency values of 97.8% and 98.5% for MTX and DOX, respectively. The adsorption kinetic of MTX and DOX via GO@Fe₃O₄@β-CD followed pseudo second-order (PSO) model, while the adsorption isotherm obeyed Langmuir model by monolayer adsorption with maximum adsorption capacities of 198.5 and 204.5 mg g⁻¹ for MTX and DOX, respectively. Therefore, it could be argued that HCl and 0.1 mol L⁻¹ NaOH would reflect adequate elution properties for GO@Fe₃O₄@β-CD recovery.
Show more [+] Less [-]Spent pot liner from aluminum industry: genotoxic and mutagenic action on human leukocytes
2019
Andrade-Vieira, Larissa Fonseca | Trento, Marcus Vinícius Cardoso | César, Pedro Henrique Souza | Marcussi, Silvana
Spent pot liner (SPL) is a toxic solid waste generated in the aluminum mining and processing industry. SPL is considered as an environmental pollution agent when is dumped on environment. Thus, it is important to access its toxicological risk for the exposed organisms. The comet assay and micronucleus test are efficient tests to detect genotoxic/mutagenic compounds by DNA damage observation. Therefore, in the present study, the genotoxic potential of SPL was evaluated through the micronucleus and comet assay on human leukocytes. After ethics committee approval (COEP—UFLA n°. CAAE 11355312.8.0000.5060), blood aliquots collected from healthy volunteers were exposed to increasing concentrations of SPL (from 0.1 to 80 g L⁻¹). All SPL treatments, including the lowest concentration applied (0.1 g L⁻¹), significantly increased the micronucleus frequency. The frequency of DNA damage was determined by visual scores (from 0 to 4) and the results were expressed on percentage of damage and arbitrary units (AU). CaCl₂ (0.01 M) was applied as negative control (NC) and doxorubicin (10 μg mL⁻¹) as positive control (PC). It was observed a dose-dependency between SPL treatments: as SPL concentration for cell incubation increases, the frequency of damage on DNA also increases. Cells incubated on the NC presented nucleoids class 0 to 2, while those exposed to SPL presents nucleoids class 0 to 4. SPL-incubated cells increasing significantly the frequency of nucleoids class 4. For the PC, the UA of damage was 267.74, which is lower than the one observed for the treatments with high doses of SPL (40–287.40 g L⁻¹ and 80–315.30 g L⁻¹). Thus, it was demonstrated that the SPL is a genotoxic agent that induces DNA damage on exposed organisms.
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