Hazard assessment of antineoplastic drugs and metabolites using cytotoxicity and genotoxicity assays.

Antineoplastic drugs are among the most toxic pharmaceuticals. Their release into the aquatic ecosystems has been reported, giving rise to concerns about the adverse effects, including cytotoxicity and genotoxicity, that they may have on exposed organisms. In this study, we analyzed the cytotoxicity and genotoxicity of 5-fluorouracil (5-FU) and its metabolite alpha-fluoro-beta-alanine (3-NH2-F); gemcitabine (GEM) and its metabolite 2'-deoxy-2',2'-difluorouridine (2-DOH-DiF); as well as cyclophosphamide (CP) on the HepG2 cell line. Drug concentrations were based on those previously observed in the effluent of a major cancer hospital in Brazil. The study found that GEM, 2-DOH-DiF and 5-FU resulted in reduced cell viability. No reduction in cell viability was observed for CP and 3-NH2-F. Genotoxic assessment revealed damage in the form of nucleoplasmic bridges for CP and 3-NH2-F. The tested concentrations of all compounds resulted in significantly increased MNi and NBUDs. The results showed that these compounds induced cytotoxic and genotoxic effects in HepG2 cells at concentrations found in the environment. To the best of our knowledge, this study is the first to report on the cytogenotoxic impacts of the metabolites 3-NH2-F and 2-DOH-DiF in HepG2 cells. These findings may help in the development of public policies that could minimize potential environmental contamination.

Detection of anti-cancer drugs and metabolites in the effluents from a large Brazilian cancer hospital and an evaluation of ecotoxicology.

The use of chemotherapy agents has been growing worldwide, due to the increase number of cancer cases. In several countries, mainly in Europe countries, these drugs have been detected in hospitals and municipal wastewaters. In Brazil this issue is poorly explored. The main goal of this study was to assess the presence of three anti-cancer drugs, 5-fluorouracil (5-FU), gemcitabine (GEM) and cyclophosphamide (CP), and two metabolites, alpha-fluoro-beta-alanine (3-NH2-F) and 2'-deoxy-2',2'-difluorouridine (2-DOH-DiF), in effluents from a large cancer hospital, in the municipal wastewater treatment plant (WWTP) influent and effluent, and also to evaluate toxicity of the mixtures of these compounds by ecotoxicological testing in zebrafish. The sample collections were performed in Barretos Cancer Hospital of the large cancer center in Brazil. After each collection, the samples were filtered for subsequent Liquid Chromatography Mass Spectrometry analysis. The presence of CP, GEM, and both metabolites (3-NH2-F and 2-DOH-DiF) were detected in the hospital wastewater and the WWTP influent. Three drugs, GEM, 2-DOH-DiF and CP, were detected in the WWTP effluent. Two drugs were detected below the limit of quantification, 2-DOH-DiF:

Effects of cannabidiol, a Cannabis sativa constituent, on oral wound healing process in rats: Clinical and histological evaluation.

The effects of cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, were assessed on oral wound healing in an in vivo model. Standardized ulcers were induced in 60 Wistar rats using a 5-mm biopsy punch on the midline of the ventral tongue. Animals received intraperitoneal injections of CBD at doses of 0 (control), 5, and 10 mg/kg daily. Animals were weighed daily, and wound healing was clinically and histologically evaluated after 3 and 7 days of treatment. CBD treatment did not influence the wound area of ulcerative lesions at either observation time. Conversely, microscopic findings revealed that at Day 3 postwounding, CBD-treated lesions exhibited significantly lower inflammatory scores than those in the control group. However, this difference was not observed at Day 7. Collectively, these findings indicate that CBD exert an antiinflammatory effect in early phase of wound healing process although it was not sufficient promote clinical improvement of oral traumatic ulcerative lesions.

Influence of radiopaque fillers on physicochemical properties of a model epoxy resin-based root canal sealer

Objective: To verify the influence of radiopaque fillers on an epoxy resin-based sealer. Material and Methods: Experimental sealers were formulated by adding 20%, 40%, 60%, 80%, 100% and 120% of calcium tungstate, ytterbium trifluoride or barium sulphate by weight to an epoxy-resin-base. Setting time, flow, film thickness, radiopacity, sorption, solubility, pH and push-out bond strength were evaluated. Results: The setting time ranged from 373 to 612.66 min, the flow varied from 13.81±0.49 to 22.49±0.37 mm, and the film thickness ranged from 16.67±5.77 to 33.33±11.54 µm. The lowest pH was 5.47±0.53, and the highest was 6.99±0.03. Radiopacity varied from 0.38±0.04 to 2.57±0.21 mmAl and increased with the amount of filler. Calcium tungstate sealers had a higher sorption and solubility than other sealers. There was no significant difference in the push-out bond strength among the fillers at the 120% concentration. CONCLUSION: The inorganic fillers evaluated and their concentrations affect the physicochemical properties of an epoxy resin-based root canal sealer. .