ISRN Toxicology最新文献

Naja sumatrana is the dominant cobra species in Malaysia, Singapore, Borneo, and Sumatra, and it does not have specific antivenom. The Haffkine antivenom has been advocated instead. This study aims to determine the efficacy of this antivenom against Naja sumatrana envenoming using a mouse model. Methods. Male Swiss albino mice were used. Intravenous LD50 was first determined separately for Naja naja and Naja sumatrana venom. ED50 was determined by preincubating antivenom with each venom at 2.5 LD50 before administering the mixture into the tail vein. Validation was carried out using a challenge test. Each mouse received 111 µg of Naja sumatrana venom intramuscularly followed by intraperitoneal administration of dilute Haffkine antivenom. Survival was recorded 24 hours after envenoming. Results. The LD50 of Naja naja venom was 78.13 µg, standard error (SE) 13.3 µg. The ED50 of the Haffkine antivenom against Naja naja venom was 45.9 mg, SE 7.5 mg. The LD50 and ED50 of Naja sumatrana venom were 55.5 µg, SE 12.0 µg; and 73.9 mg, SE 12.0 mg, respectively. The intra-peritoneal ED50 against 111 µg intramuscular Naja sumatrana venom was 136.95 mg, SE 36.74 mg. Conclusion. The Haffkine polyvalent antivenom exhibited cross-neutralisation against Naja sumatrana venom when used at a higher dose.

Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, biosensors, food additives, pigments, rubber manufacture, and electronic materials. With the wide application of ZnO-NPs, concern has been raised about its unintentional health and environmental impacts. This study investigates the toxic effects of ZnO-NPs in human lung cells. In order to assess toxicity, human lung epithelial cells (L-132) were exposed to dispersion of 50 nm ZnO-NPs at concentrations of 5, 25, 50, and 100  μ g/mL for 24 h. The toxicity was evaluated by observing changes in cell morphology, cell viability, oxidative stress parameters, DNA damage analysis, and gene expression. Exposure to 50 nm ZnO-NPs at concentrations between 5 and 100  μ g/mL decreased cell viability in a concentration-dependent manner. Morphological examination revealed cell shrinkage, nuclear condensation, and formation of apoptotic bodies. The oxidative stress parameters revealed significant depletion of GSH level and increase in ROS levels suggesting generation of oxidative stress. ZnO-NPs exposure caused DNA fragmentation demonstrating apoptotic type of cell death. ZnO-NPs increased the expression of metallothionein gene, which is considered as a biomarker in metal-induced toxicity. To summarize, ZnO-NPs cause toxicity in human lung cells possibly through oxidative stress-induced apoptosis.

Diesel exhaust emission is a major health concern because of the complex nature of its gaseous content (e.g., NO2, NO, CO, and CO2) and high concentration of particulate matter (PM) less than 2.5  μ m which allows for deeper penetration into the human pulmonary system upon inhalation. The aim of this research was to elucidate the potential toxic effects of diesel exhaust on a human pulmonary-based cellular system. Validation of a dynamic direct exposure method for both laboratory (230 hp Volvo truck engine) and field (Volkswagen Passat passenger car) diesel engines, at idle mode, was implemented. Human pulmonary type II epithelial cells (A549) grown on porous membranes were exposed to unmodified diesel exhaust at a low flow rate (37.5 mL/min). In parallel, diesel emission sampling was also conducted using real-time air monitoring techniques. Induced cellular effects were assessed using a range of in vitro cytotoxicity assays (MTS, ATP, and NRU). Reduction of cell viability was observed in a time-dependent manner following 30-60 mins of exposure with NRU as the most sensitive assay. The results suggest that the dynamic direct exposure method has the potential to be implemented for both laboratory- and field-based in vitro toxicity studies of diesel exhaust emissions.

The toxicity of arsenic in soil and ground water is one of the most important environmental problems particularly in South-East Asia. Arsenic-polluted irrigation water creates hazard in soil environment and also in crop quality. In the present study, response of black gram (Vigna mungo L.) to arsenic with or without phosphate application was investigated. Arsenic-treated plants showed reduction in their growth and pigment content. Arsenic significantly enhanced lipid peroxidation, electrolyte leakage, and level of proline showing oxidative stress. Arsenic toxicity was associated with an increase in the activities of antioxidative enzymes like superoxide dismutase, peroxidase, and ascorbate peroxidase whereas catalase activity decreased at higher arsenic dose. Joint application of phosphate with arsenic resulted in significant alterations in most of the parameters tested under the purview of arsenic treatment alone which lead to better growth in black gram.

In September 2012, the Medicines and Healthcare products Regulatory Agency (MHRA) substantially amended the Marketing Authorisation for acetylcysteine following an extensive review. The present study examined the impact of this license change on patterns of acetylcysteine use in patients presenting to hospital after paracetamol (acetaminophen) overdose. Between September 2011 and April 2013, 785 consecutive patients presented to York Hospital due to paracetamol overdose, and a before-after analysis was used to compare outcomes. There were 483 patients before and 302 patients after the license amendment, and age, gender, acute or staggered overdose pattern, and dose were similar in both groups. In the patients with paracetamol concentrations between the "100-line" and "200-line," a significantly higher proportion received acetylcysteine treatment (51% before versus 98% after, P = 0.0029), as expected. A modest increase was also observed in relation to late or staggered overdose or cases where the time of ingestion was uncertain (53% versus 74%, P = 0.0430). The median duration of hospital stay increased across the entire study population, from 15 to 24 hours (P = 0.0159) due to the increased proportion of patients requiring acetylcysteine treatment. The findings indicate that the MHRA amendment is a financially costly intervention, and further studies are needed to examine clinical outcomes so that its cost effectiveness might be addressed.

Increasing application of engineered nanomaterials within occupational, environmental, and consumer settings has raised the levels of public concern regarding possible adverse effects on human health. We applied a tiered testing strategy including (i) a first in vitro stage to investigate general toxicity endpoints, followed by (ii) a focused in vivo experiment. Cytotoxicity of laboratory-made functionalized multiwalled carbon nanotubes (CNTs) (i.e., MW-COOH and MW-NH2), compared to pristine MWCNTs, carbon black, and silica, has been assessed in human A549 pneumocytes by MTT assay and calcein/propidium iodide (PI) staining. Purity and physicochemical properties of the test nanomaterials were also determined. Subsequently, pulmonary toxic effects were assessed in rats, 16 days after MWCNTs i.t. administration (1 mg/kg b.w.), investigating lung histopathology and monitoring several markers of lung toxicity, inflammation, and fibrosis. In vitro data: calcein/PI test indicated no cell viability loss after all CNTs treatment; MTT assay showed false positive cytotoxic response, occurring not dose dependently at exceedingly low CNT concentrations (1  μ g/mL). In vivo results demonstrated a general pulmonary toxicity coupled with inflammatory response, without overt signs of fibrosis and granuloma formation, irrespective of nanotube functionalization. This multitiered approach contributed to clarifying the CNT toxicity mechanisms improving the overall understanding of the possible adverse outcomes resulting from CNT exposure.

Medicinal plants are still widely used worldwide; yet for some species, little or no information is available concerning their biological activity, specially their genotoxic and antimutagenic potential. Mikania laevigata (Asteraceae) is a native plant from South America, and its extracts are largely used to treat respiratory complaints. The aim of the present work was then to evaluate, in vivo, the potential biological activity of M. laevigata on the genotoxicity induced by methyl methanesulfonate (MMS) and cyclophosphamide (CP), using the comet assay. Male CF1 mice were divided into groups of 5-6 animals, received by gavage 0.1 mL/10 g body wt of water, Mikania laevigata extract (MLE), MMS, and CP. Results showed that treatment with 200 mg/kg of the MLE previously to MMS and CP administration, respectively, reduced the damage index (DI) in 52% and 60%, when compared to DI at 24 h. Pretreatment also reduced the damage frequency (DF) in 56% (MMS) and 58% (CP), compared to DF at 24 h. MLE administration has been shown to protect mouse DNA from damage induced by alkylating agents; this corroborates to the biological activities of M. laevigata and points towards the need of plant compounds isolation to proceed with further studies.

NUTRALYS Pea Protein Isolate, a protein supplement, is a high-quality source of protein which is primarily emulsifying functional protein. We evaluated the genotoxic potential of NUTRALYS isolated from dry yellow pea, using three established genotoxicity tests (AMES test in vitro chromosomal aberration test, and in vivo micronucleus test) employing OECD guidelines under GLP conditions. In the bacterial reverse mutation test, NUTRALYS did not show positive responses in strains detecting point and frame shift mutations. In the chromosomal aberration test, NUTRALYS did not induce chromosome aberrations in the presence and absence of metabolic activation. In the bone marrow micronucleus test, NUTRALYS did not induce significant increases of micronucleated immature (polychromatic) erythrocytes in bone marrow of test animals.

The role of voltage-dependent Ca channels (VDCC) in the membrane permeation of two toxic metals, lead (Pb) and cadmium (Cd), was studied in mammalian cells. Both metals interact with Ca-binding sites, but, while Cd influx appears to occur mainly through the same pathways as Ca, Pb is also rapidly taken up by different passive transport systems. Furthermore, I compared the effect of Cd in two Chinese hamster ovary (CHO) cell lines, a wild-type and a modified cell line, which were permanently transfected with an L-type VDCC. When cultures were subjected to a brief (30-60 min) exposure to 50-100  μ M Cd, apoptotic features, metal accumulation, and death were comparable in both cell lines although, in transfected cells, the effect of Cd treatment was partially prevented by nimodipine (VDCC antagonist) and enhanced by BayK8644 (VDCC agonist). Thus, expression of L-type Ca channels is not sufficient to modify Cd accumulation and sensitivity to a toxicological significant extent and while both Cd and Pb can take advantage of VDCC to permeate the membrane, these transport proteins are not the only, and frequently not the most important, pathways of permeation.