Hematotoxicity of bacillus thuringiensis as spore-crystal strains cry1aa, cry1ab, cry1ac or cry2aa in swiss albino mice

Formulated and sporulated cultures of Bacillus thuringiensis (Bt) have been widely used against insect pests, but after the advent of genetically modified plants expressing δ-endotoxins, the bioavailability of Cry proteins has been increased. For biosafety reasons their adverse effects should be studied, mainly for non-target organisms. Thus, we evaluated, in Swiss albino mice, the hematotoxicity and genotoxicity of four Bt spore-crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac or Cry2A, administered alone by gavage with a single dose of 27 mg/ Kg, 136 mg/Kg or 270 mg/Kg, 24 h, 72 h or 7 days before euthanasia. Binary combinations of these four spore-crystal proteins were also assayed at 270 mg/Kg with a single administration 24 h before euthanasia. Control mice received filtered water or cyclophosphamide at 27 mg/kg. For hematotoxicity evaluations, blood samples were drawn by cardiac puncture and processed in a multiple automated hematology analyzer; for genotoxicity analyses, micronucleus test was carried out in mice bone marrow cells. Spore-crystal administrations provoked selective hematotoxicity for the 3 exposure times, particularly for erythroid lineage. A significant reduction in bone marrow cell proliferation demonstrated cytotoxic but not genotoxic effects. These effects persisted for all exposure times, becoming more evident at 7 days. Similar results were observed for binary combinations at 24 h, suggesting that further studies are required to clarify the mechanism involved in the hematotoxicity found in mice, and to establish the toxicological risks to non-target organisms, especially mammals, before concluding that these microbiological control agents are safe for mammals

Magnetic resonance investigation of magnetic-labeled baker's yeast cells

In this study, the interaction of DMSA-coated magnetite nanoparticles (5 and 10 nm core-size) with Saccharomyces cerevisae was investigated using magnetic resonance (MR) and transmission electron microscopy (TEM). The TEM micrographs revealed magnetite nanoparticles attached externally to the cell wall. The MR data support the strong interaction among the nanoparticles supported by the cells. A remarkable shift in the resonance field was used as signature of particle attachment to the cell wall

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

Background: Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods: Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results: Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions: In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications

Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells

Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays) and in mice (micronucleus assays). Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage

Successful Strategy for Targeting the Central Nervous System Using Magnetic Albumin Nanospheres

This study reports on the successful use of magnetic albumin nanosphere (MAN), consisting of maghemite nanoparticles hosted by albumin-based nanosphere, to target different sites within the central nervous system (CNS). Ultrastructural analysis by transmission electron microscopy (TEM) of the material collected from the mice was performed in the time window of 30 minutes up to 30 days after administration. Evidence found that the administered MAN was initially internalized and transported by erythrocytes across the blood-brain-barrier and transferred to glial cells and neuropils before internalization by neurons, mainly in the cerebellum. We hypothesize that the efficiency of MAN in crossing the BBB with no pathological alterations is due to the synergistic effect of its two main components, the iron-based nanosized particles and the hosting albumin-based nanospheres. We found that the MAN in targeting the CNS represents an important step towards the design of nanosized materials for clinical and diagnostic applications.CAPESCAPESMCT/CNPqMCT/CNPqFINEPFINEPFINATECFINATECFAPDFFAP-DFFAPESPFAPES