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The aim of this work was to develop nanosuspensions of praziquantel (PZQ) and to evaluate their influence on the energetic metabolism of cysticerci inoculated in BALB/c mice. We analyzed metabolic alterations of glycolytic pathways and the tricarboxylic acid cycle in the parasite. The nanosuspensions were prepared by precipitation and polyvinyl alcohol (PVA), poloxamer 188 (P188) and poloxamer 407 (P407) were used as stabilizers. Nanosuspension prepared with PVA had a particle size of 100 nm, while P188- and P407-based nanosuspensions had particle sizes of 74 nm and 285 nm, respectively. The zeta potential was −8.1, −8.6, and −13.2 for the formulations stabilized with PVA, P188 and P407, respectively. Treatments of T. crassiceps cysticerci-infected mice resulted in an increase in glycolysis organic acids, and enhanced the partial reversion of the tricarboxylic acid cycle, the urea cycle and the production of ketonic bodies in the parasites when compared to the groups treated with conventional PZQ. These data suggest that PZQ nanosuspensions greatly modified the energetic metabolism of cysticerci in vivo. Moreover, the remarkable metabolic alterations produced by the stabilizers indicate that further studies on nanoformulations are required to find potentially suitable nanomedicines. [ABSTRACT FROM AUTHOR]

Abstract Schistosomiasis is a disease that affects tropical and subtropical areas and is considered the second most prevalent parasitic disease in the world. One of the ways of combating this disease is the use of molluscicidal agents to eliminate or reduce the population of intermediate host snails. Polyhexamethylene biguanide hydrochloride (PHMB) is a chemical biocide commonly used as a disinfectant and antiseptic in the food industry and very successfully for the disinfection of swimming pools. The US Environmental Protection Agency (USEPA) indicated the PHMB as low environmental risk. The present study aimed to evaluate the molluscicidal activity of the PHMB in freshwater snail (Biomphalaria glabrata), intermediate host of Schistosoma mansoni. The PHMB showed high toxicity against all stages of the snail B. glabrata : embryos, new-borns and adults. The LC 50 estimated was 0.98 mg L−1; 1.43 mg L−1 and 1.49 mg L−1, respectively, after exposure of 144 h for embryos and 96 h for new-borns and adults. PHMB did not prevent the development of embryos within the egg mass, since at all concentrations evaluated 80% of the embryos managed to develop until the hypo-stage, which is the last stage of development before hatching. However, PHMB inhibited the hatching of embryos by 100% at all concentrations above 1.6 mg L−1. PHMB proved to be a promising substance in the fight against schistosomiasis by eliminating the intermediate host (B. glabrata). This was the first study that makes an experimental observation of the molluscicidal activity of PHMB. Graphical abstract Image Highlights • Morphological changes in B. glabrata embryos after exposure to PHMB. • Toxicity of PHMB to new-borns and adult B. glabrata is dependent concentration. • Behavioural changes in adults of B. glabrata after exposure to PHMB. • PHMB is a potential molluscicide. [ABSTRACT FROM AUTHOR]

Although iron oxide nanoparticles (IONPs) have been widely used in nanomedicine and nanoremediation, their ecotoxicological effects on aquatic organisms remain unclear. In this study, the melanomacrophage center (MMC) response and hepatic histopathologic biomarkers were investigated in female guppies, Poecilia reticulata , exposed to citrate-functionalized IONPs (γ-Fe 2 O 3 ) at an environmentally relevant iron concentration (0.3 mg L −1 ) over 21 days. The animals were collected at the beginning of the experiment and after 3, 7, 14, and 21 days of exposure. Guppies exposed to IONPs showed increases in the number, area, and perimeter of MMC when compared with the unexposed ones, especially after 7 days of exposure. The results showed an increase in the frequency of histopathologic changes in fish after 7 days of exposure to IONPs, such micro- and macro-vesicular steatosis, melanomacrophage aggregates, exudate, and hemorrhagic foci. The acute (3 and 7 days) and long-term (14 and 21 days) exposure of P. reticulata to IONPs induced high histopathologic indexes associated with circulatory disorders and inflammatory responses. Results showed that the MMC response and histopathologic index are important biomarkers to indicate the environmental impact of IONPs, confirming that the guppy P. reticulata is a target of ecotoxicity of IONPs. [ABSTRACT FROM AUTHOR]

• Gonad of freshwater snails is target for iron oxide nanoparticles and FeCl 3 toxicity • Both iron forms induced gonadal histopathological changes • GLA-IONPs induced higher vacuolated vitellogenic oocytes when compared to FeCl 3 GLA-IONPs induced higher vacuolated vitellogenic oocytes when compared to FeCl 3 • Reproductive toxicity induced by GLA-IONPs and FeCl 3 in B. glabrata Considering that most animals in an aquatic ecosystem are invertebrates, concerns about the ecotoxicological impact of emerging pollutants, such as nanomaterials, in these populations are relevant, which can lead to loss of aquatic biodiversity. However, knowledge concerning the effects of iron-based nanoparticles (IONPs) at cell and tissue-levels on freshwater gastropods remains limited. Thus, the present study aimed to analyse the histopathological changes and inflammatory response in the freshwater snail Biomphalaria glabrata after chronic exposure to gluconic-acid functionalized IONPs (GLA-IONPs) in comparison with their dissolved counterpart (FeCl 3). Snails were exposed to both iron forms (1.0, 2.5, 6.25, and 15.62 mg L−1) for 28 days, and the qualitative and quantitative histopathological assessment on hermaphrodite gonads was conducted, following by analysis of histopathological indices and inflammatory responses. Results showed that both iron forms (GLA-IONPs and FeCl 3) induced several gonadal histopathologies in the snails, mainly atresic acini, vacuolization of pre-vitellogenic oocytes, and atresic oocytes in a concentration-dependent pattern. GLA-IONPs induced a more intense inflammatory response and high frequency of vacuolized vitellogenic oocytes in comparison with FeCl 3. Environmentally relevant concentration (2.5 mg L−1) of GLA-IONPs and FeCl 3 induced high gonadal histopathological indices, indicating their potential reproductive toxicity. The current study showed that the chronic exposure of snails to GLA-IONPs and their dissolved counterpart (FeCl 3) induced several gonadal histopathological changes and inflammatory responses in B. glabrata , confirming their potential risk to aquatic biodiversity. [Display omitted] [ABSTRACT FROM AUTHOR]

• Differential bioaccumulation of iron oxide nanoparticles (IONPs) and Fe3+ in B. glabrata. • Reproductive toxicity induced by chronic exposure to IONPs. • Chronic exposure to IONPs induced behavior impairments in B. glabrata. • The exposure of adult snails to IONPs decreased the fecundity and fertility. • B. glabrata as study model to assess the environmental risk of IONPs. Iron oxide nanoparticles (IONPs) have been applied in several sectors in the environmental field, such as aquatic nanoremediation, due to their unique superparamagnetic and nanospecific properties. However, the knowledge of chronic toxicity of IONPs on aquatic invertebrate remains limited. Thus, the present study aimed to analyze the chronic toxicity of gluconic acid-functionalized IONPs (GLA-IONPs) and their dissolved counterpart (FeCl 3) to freshwater snail Biomphalaria glabrata. GLA-IONPs were synthesized and characterized by multiple techniques, and the snails were exposed to both Fe forms at environmentally relevant concentrations (1.0–15.6 mg L−1) for 28 days. The bioaccumulation, mortality rate, behavior impairments, morphological alterations, fecundity and fertility of snails were analyzed. Results showed that GLA-IONPs induced high iron bioaccumulation in the entire soft tissue portion. Chronic exposure to GLA-IONP increased the behavioral impairments of snails compared to iron ions and control groups. Both Fe forms reduced the fecundity, while the mortality and reduced fertility were observed only after the exposure to GLA-IONPs at 15.6 mg L−1. Overall results indicated the behavioral impairments and reproductive toxicity associated, possibly, to bioaccumulation of GLA-IONPs in the B. glabrata. These results can be useful for the development of eco-friendly nanotechnologies. [ABSTRACT FROM AUTHOR]

The emerging growth of nanotechnology has attracted great attention due to its application in the parasite and intermediate host control. However, the knowledge concerning the mechanism of action (MoA) and toxicity of nanomaterials (NMs) to snails remain unclear. In this context, the present study revised the historical use of snails as experimental models in nanotoxicological studies and summarized the MoA and toxicity of NMs in aquatic and land snails. The data concerning the bioaccumulation, reproductive and transgenerational toxicity, embryotoxicity, genotoxicity and potential molluscicidal activity of NMs were revised. Furthermore, the data about the experimental conditions, such as exposure time, concentrations, cell and tissue-specific responses, snail species and nanoparticle types are discussed. Revised data showed that the toxic effects of NMs were reported for 21 snail species with medical, veterinary and ecological importance. The NM toxicity to snails is dependent on the physical and chemical properties of NMs, as well as their environmental transformation and experimental design. The NM bioaccumulation on snails was related to several toxic effects, such as reactive oxygen species (ROS) production, oxidative stress, following by oxidative damage to DNA, lipids and proteins. The NM metabolism in snails remains unknown. Results showed the potential use of NMs in the snail control program. Also, significant research gaps and recommendations for future researches are indicated. The present study confirms that snails are suitable invertebrate model system to assess the nanotoxicity. Image 1 • State-of-the-art review of the nanomaterial (NM) toxicity in snails. • Mechanism of action and toxicity of NMs in snails are revised. • NMs as potential molluscicide. • Snail as suitable model system to assess the NM toxicity. [ABSTRACT FROM AUTHOR]

• Ag NPs toxicity is developmental stage dependent. • Morphological alterations in B. glabrata embryos after exposure to Ag NPs. • Ag NP toxicity to embryos and newly-born snails is concentration dependent. • Ag NPs is a potential molluscicide. Silver nanoparticles (Ag NPs) have been applied in several commercial products due to their antimicrobial properties, while their molluscicide properties, mode of action and toxicity to snail species remain unclear. In this study, the comparative toxicity of polyvinylpyrrolidone (PVP)-functionalized Ag NPs and their dissolved counterpart (Ag ions) was analyzed during the early developmental stages of the freshwater snail Biomphalaria glabrata , intermediate host of Schistosoma mansoni. Ag NPs were synthesized and characterized by multiple techniques, and the snail embryotoxicity was analyzed in terms of mortality, hatching, developmental stages and morphological alterations, while the acute toxicity to newly-hatched snails was analyzed by mortality and behavioral impairments. Results showed that both Ag forms induced mortality, hatching delay and morphological alterations (especially hydropic abnormalities) in snail embryos in a concentration and exposure time dependent patterns. Ag NPs showed low embryotoxic effects and similar toxicity for newly-hatched snails when compared to their dissolved counterparts, indicating that the nanotoxicity was dependent of snail developmental stages. The knowledge about the Ag NP toxicity to different early development stages of B. glabrata contributes to its potential use as molluscicide and control of neglected tropical diseases, including schistosomiasis. Image, graphical abstract [ABSTRACT FROM AUTHOR]