Toxic, cytotoxic and genotoxic effect of plumbagin in the developmental stages of Biomphalaria glabrata (Say, 1818-intermediate host) and cercaricidal activity against the infectious agent of schistosomiasis mansoni.

BACKGROUND: Snails of the genus Biomphalaria are intermediate hosts of Schistosoma mansoni, the main etiological agent of schistosomiasis mansoni, which affects about 236.6 million people in tropical and subtropical regions of the world. The World Health Organization recommends the population control of vector snails as one of the strategies to reduce the prevalence and incidence of schistosomiasis. In this study, molluscicidal and antiparasitic activities of plumbagin, a naturally sourced naphthoquinone with a range of biological effects, were evaluated against B. glabrata and cercariae of S. mansoni. RESULTS: After 24 h of exposure, plumbagin demonstrated molluscicidal activity at low concentrations against embryos (LC50 of 0.56, 0.93, 0.68, 0.51 and 0.74 µg mL-1 for the blastula, gastrula, trochophore, veliger and hippo stage, respectively) and adult snails (LC50 of 3.56 µg mL-1 ). There were no changes in exposed snails' fecundity or fertility; however, plumbagin was able to increase the frequency of DNA damage and the number of hemocytes, with apoptosis and binucleation being the main hemocyte alterations. In addition, plumbagin showed death of S. mansoni cercariae in the concentration of 1.5 µg mL-1 in 60 min, while showing moderate toxicity to Artemia salina. CONCLUSION: Plumbagin proved to be a promising substance for the control of B. glabrata population, intermediate host of S. mansoni, as well as the cercariae, infective stage for humans (definitive host), while being moderately toxic to A. salina, a crustacean widely used in ecotoxicity tests. © 2022 Society of Chemical Industry.

The Natural Compound Hydrophobic Usnic Acid and Hydrophilic Potassium Usnate Derivative: Applications and Comparisons.

Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.

Toxicity and genotoxicity of domestic sewage sludge in the freshwater snail Biomphalaria glabrata (Say, 1818).

Waste produced in homes is one of the main sources of pollutants in freshwater ecosystems. Therefore, it is imperative to implement methodologies that aid in environmental monitoring procedures. The use of organisms as biomonitors has grown increasingly prevalent as they are models that provide data that can be adequately evaluated. In this work, we investigated the genotoxic and cytotoxic effects caused by domestic sewage sludge through an analysis of biomarkers in the mollusk Biomphalaria glabrata. For the tests, increasing concentrations of 50, 100, 150, and 500 mg L-1 of domestic sewage sludge were standardized, in addition to control groups. Assays were performed after the mollusks were exposed to the domestic sewage sludge in acute (48 h) and chronic (15 d) manner. Toxicity tests were performed with embryonic and adult snails. The cytoplasmic and nuclear changes were analyzed in the hemocyte cells. Lastly, genotoxic damage was analyzed using the comet assay. Adult snails and embryos of B. glabrata showed no significant morphological changes. Domestic sludge caused deleterious effects on mollusks as confirmed after cell genotoxicity tests. Therefore, based on the results obtained from the analysis of B. glabrata hemocytes, we can affirm that domestic sewage sludge causes genotoxic and cytotoxic effects on mollusk cells. Therefore, it is possible to conclude that the mollusk Biomphalaria glabrata can be used as a good low-cost alternative to assist in the biomonitoring of freshwater environments. Graphical Abstract.

Study of genotoxic and cytotoxic effects after acute and chronic exposures to industrial sewage sludge on Biomphalaria glabrata hemocytes.

Industrial development has provided numerous benefits to improve quality of life in modern times, however, it has also led to the development and use of a large number of toxic chemicals which have caused damage to various ecosystems. Consequently, knowledge of techniques and organisms that can be used to monitor, identify and quantify environmental pollutants has become increasingly relevant. Therefore, the objective of this study was to use the mollusk Biomphalaria glabrata to analyze biomarker and biomonitoring parameters of industrial sewage sludge. To perform the tests, concentrations of 50, 100, 150 and 500 mg L-1 of industrial sewage sludge were standardized. All the tests were performed after the animals were exposed to the sludge in acute and chronic forms. Embryos exposure to sludge did not show a significant percentage of the animals non-viable when compared to the control group. Subsequently, hemocytes were analyzed for the presence of cytoplasmic and nuclear alterations. Finally, the comet test was performed to quantify the genotoxic damage caused by exposure to industrial sludge. Analysis hemocytes showed a significant number of cellular alterations was observed, mainly due to the high frequency of apoptosis. Moreover, during the analysis of nucleoids several degrees of nuclear damage were identified, with the groups exposed to the highest concentrations presenting the greatest genotoxic damage. Thus, we can conclude that the parameters evaluated in the mollusk Biomphalaria glabrata have proven to be a good tool, along with other techniques and complementary organisms, to assist aspects related to biomonitoring of freshwater ecosystems.

Toxicological effects of Ramalina aspera (lichen) on Biomphalaria glabrata snails and Schistosoma mansoni cercariae.

In this study, the molluscicidal activities against Biomphalaria glabrata and cercaricidal activities against Schistosoma mansoni of the ether extract of Ramalina aspera were evaluated. Additionally, toxicity parameters were evaluated at sublethal doses in terms of the influence of the extract on the fertility and fecundity of snails, as well as morphological alterations and quantification of their immunological cells. A test with Artemia salina was also carried out, in order to verify the environmental toxicity of the compound. The ether extract of R. aspera, in which divaricatic acid was identified as the major compound, demonstrated molluscicidal activity at low concentrations against both embryos (LC90 of 22.78, 24.23, 16.63 and 16.03 µg mL-1 for the gastrula, blastula, trochophore and veliger, respectively) and against adult snails (LC90 of 8.66 µg mL-1), after 24 h of exposure. At the sublethal doses, it was possible to observe a decrease in fecundity and quantitative and morphological changes in the defense cells of the exposed snails. In addition, the extract of R. aspera showed a cercaricidal effect on S. mansoni from the concentration of 5.0 µg mL-1, while showing low toxicity to Artemia salina. The ether extract of R. aspera demonstrated effective molluscicidal activity on embryos and adult snails of the species B. glabrata, cercariae of S. mansoni, and presenting low toxicity on Artemia salina. In this way, it could be considered a promising compound in the development of future molluscicidal and cercaricidal agents, thus helping to combat schistosomiasis.

Cytotoxic and genotoxic effect of oxyfluorfen on hemocytes of Biomphalaria glabrata.

Chemicals released from anthropogenic activities such as industry and agriculture often end up in aquatic ecosystems. These substances can cause serious damage to these ecosystems, thus threatening the conservation of biodiversity. Among these substances are pesticides, such as oxyfluorfen, a herbicide used for the control of grasses and weeds. Considering its widespread use, it is important to investigate the possible toxicity of this compound to aquatic organisms, especially invertebrates. Hence, the use of biological systems able to detect such effects is of great importance. The mollusk Biomphalaria glabrata has been shown to be useful as an environmental indicator to assess the potential ecological effects of physical and chemical stressors in freshwater environments. The present study sought to detect mutagenic changes in hemocytes of B. glabrata exposed to oxyfluorfen. To perform these tests, this study used ten animals per group, exposed acutely (48 h) and chronically (15 days) to oxyfluorfen. The herbicide concentrations were 0.125, 0.25, and 0.5 mg/L. The results showed that oxyfluorfen induced significant frequencies of micronuclei, binucleated cells, and apoptosis in hemocytes of mollusks when compared to the control group. Unlike chronic exposure, acute exposure was dose-dependent. The present study's results demonstrate the cytotoxic and genotoxic effects of oxyfluorfen on hemocytes of B. glabrata.

Study of the Potential Radiomitigator Effect of Quercetin on Human Lymphocytes.

Several substances of synthetic and natural origin have been studied to determine their ability to protect the body from damage caused by ionizing radiation. Among these substances, quercetin has been shown to be a naturally occurring molecule with high radioprotective and radiomitigator potential due to its antioxidant properties. The objective of this work was to ascertain the potential radiomitigator effect of quercetin on chromosome aberration yield in lymphocytes of in vitro-irradiated human peripheral blood. At first, the DPPH (2,2-diphenyl-1-picryl-hydrazyl) radical capture test was performed to determine the antioxidant activity of quercetin and to select the concentrations to be tested. The blood was irradiated at doses of 2.5, 3.5, and 4.5 Gy and lymphocytes were cultured with quercetin at preselected concentrations of 37.5 and 75 µM. Then, the slides were prepared for scoring unstable chromosome aberrations (dicentrics, rings, and fragments). The results showed that the lymphocytes irradiated and later exposed to quercetin presented a lower frequency of chromosomal alterations compared to the control sample which was irradiated and not exposed to quercetin. The results suggest a potential radiomitigator effect of the flavonoid quercetin on human lymphocytes exposed, in vitro, to ionizing radiation. This effect may be related to decrease in the release of cytokines (INF-γ, PGE2, IL-1ß, IL6, IL-8) involved in the proinflammatory processes as well as downregulation of NF-kB and reduction of expression TGF-ß.

Barbatic Acid Offers a New Possibility for Control of Biomphalaria Glabrata and Schistosomiasis.

This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained by successive extractions with diethyl ether. The obtained extracts were analyzed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (¹H-NMR) and infrared (IR) spectroscopy. The results demonstrated that the ether extract exerted embryotoxic effects at 50 and 100 µg/mL and molluscicidal effects at 20 and 25 µg/mL. BAR exhibited no embryotoxicity, and its molluscicidal concentration was equal to that of the ether extract. However, after 60 min of exposure, 1 µg/mL BAR presented cercaricidal activity against the parasite S. mansoni at the second larval stage. Neither substance induced toxicity against A. salina. These results indicate the potential molluscicidal activities of the ether extract and BAR against B. glabrata and S. mansoni cercariae. In addition to these effects, there was a lack of toxicity against the aquatic environment and no damage to the biota, indicating the potential of these products for large-scale control and/or eradication of schistosomiasis.