Can the exposure system adopted influence the results of the atrazine toxicity in hepatic tissue of fish?

The widespread use of atrazine, a herbicide used to control weeds, has contributed to the increased contamination of aquatic environments. To assess the toxicological effects of a xenobiotic on a nontarget organism in the laboratory, different models of toxicological exposure systems have been widely used. Therefore, the aim of this study was to evaluate and compare the action of sublethal concentrations of atrazine on the hepatic histology of Oreochromis niloticus, considering two models of exposure: static (where atrazine was only added once) and semi-static (where atrazine was periodically renewed). Fish were exposed to a concentration of 2 ppm atrazine for 15 days, which was verified by high-performance liquid chromatography. The livers were stained with hematoxylin and eosin and histopathological data were collected. In addition, they were submitted to immunohistochemistry for inducible nitric oxide synthase (iNOS). A maximum variation of 45% (static) and 12.5% (semi-static) was observed between the observed and nominal atrazine concentration. Nuclear and cytoplasmic changes were observed in both experimental models. Hepatocytes from the livers of the static system showed a degenerative appearance, while in the semi-static system, intense cytoplasmic vacuolization and necrosis were observed. iNOS positive cells were identified only in macrophages in the hepatocytes of fish in the semi-static system. These results directly showed how the choice of exposure system can influence the results of toxicological tests. However, future analysis investigating the by-products and nitrogen products should be carried out since the histopathological findings revealed the possibility of these compounds serving as secondary contamination routes.

Evaluation of the potential environmental risk from the destination of medicines: an epidemiological and toxicological study.

BACKGROUND: The high consumption of medicines by the population and their storage at home might cause an increase in the number of pharmaceutical substances that may be inappropriately discarded in the sanitary sewage, reaching an environmental aquatic. Thus, the effects of these emerging contaminants need more studies. OBJECTIVES: To identify the profile of most medicines that are discarded by users of community pharmacy and evaluate the toxicity of the most disposed drugs. METHODS: This was a translational study. A descriptive observational study was carried out for convenience of community pharmacy users using a standardized questionnaire. Subsequently, the lethal concentration 50 (LC50) for medicine that is most frequently discarded was determined. After LC50, the embryos (n = 144) were exposed to sublethal concentrations for most discarded drug at 24, 48, and 72 h. Mortality, heartbeat, and embryo deformities were used as parameters of toxicity. RESULTS: Most respondents (96%) had a "home pharmacy." The primary forms of disposal were in the common household waste, kitchen sink, and/or bathroom. The medicines that were most incorrectly discarded by the interviewees were nimesulide (17.1%), dipyrone (10.7%), and paracetamol (5.2%). LC50 of nimesulide was calculated (0.92 µgmL-1). The toxicological test revealed that embryos exposed to nimesulide showed several abnormalities, such as defects in the spinal cord, tail, yolk sac, as well as pericardial edema. Furthermore, the heartbeat decreased by 30% at a concentration of 0.4 µgmL-1 as compared with control group. The yolk sac and pericardial areas increased to >100% in all treatment groups when compared with the control group. CONCLUSION: Respondents disposed medicines in an inappropriate manner primarily in household waste and in the toilet. Nimesulide was the most discarded drug according to study population. Moreover, teratogenic effects such as spinal cord defects, decreasing heartbeats, and increasing pericardial and yolk sac area in embryos were observed after exposure to nimesulide. These results show that nimesulide may promote risk to aquatic organisms and to human health if it is discarded in an unsafe manner.

Involvement of Src signaling in the synergistic effect between cisplatin and digoxin on cancer cell viability.

Cisplatin and other platinum-containing drugs have played a crucial role in anticancer treatments for over 30 years. However, treatment with cisplatin may cause serious side effects, such as myelosuppression, nausea, ototoxicity, nephrotoxicity, and cell resistance processes. In addition, cardiotonic steroids, particularly digoxin, have recently been suggested to exert potent anticancer effects. Therefore, it is possible that the combined treatment of HeLa cells with cisplatin and digoxin can ameliorate the cytotoxic effects and decrease the side effects of cisplatin. In this study, we demonstrated that the interaction between cisplatin and digoxin had a synergistic effect on cervical cancer cells and a significantly positive cytotoxic and antiproliferative effect on this cell line compared to the control and single cisplatin treatments. Although a decrease in the Na,K-ATPase α1 subunit expression was observed in total extracts, its expression remains unchanged in the membrane, as does the Na,K-ATPase activity. The antiproliferative effect of the synergistic treatment appears to depend on Src kinase activation, indicating the possible involvement of the Scr-EGFR-ERK1/2 pathway in the antitumor effect. The inhibition of ERK1/2 provoked the same synergism with 1 µM cisplatin as that observed with 1 nM digoxin plus 1 µM cisplatin but not with 1 nM digoxin. Pretreatment with PP2 during combined treatment abolished the synergistic effect on the antiproliferative activity. Cisplatin and digoxin are already used in the clinical setting; therefore, this study opens possibilities for future clinical trials of combined treatments to improve treatment outcomes with a lower incidence of toxicity and side effects.