Biocompatibility of marine magnetotactic ovoid strain MO-1 for in vivo application

Magnetotactic bacteria are capable of biosynthesizing magnetic nanoparticles,also called magnetosomes,and swimming along magnetic field lines.The abilities endow the whole cells of magnetotactic bacteria with such applications as targeted therapy and manipulation of microrobots.We have shown that the intact marine magnetotactic bacteria MO-1 kill efficiently antibiotic-resistant pathogen Staphylococcus aureus in vivo,but the biocompatibility of this marine bacterium is unknown.In this study,the strain MO-1 was chosen to analyze its biocompatibility and potential for biomedicine applications.Results showed that MO-1 cells could be guided at 37℃ under an external magnetic field and swim in the blood plasma and urine.They could keep active locomotivity within 40 min in the plasma and urine,although their velocity slowed down.When incubated with human cells,magnetotactic bacteria MO-1 had no obvious effects on cellular viability at low dose,while the cell toxicity increased with the augmentation of the quantity of the MO-1 cells added.In the in-vivo experiments,the median lethal dose of magnetotactic bacteria MO-1 in rats was determined to be 7.9×10^(10) bacteria/kg.These results provided the foundation for the biocompatibility and safety evaluations of magnetotactic bacteria MO-1 and suggested that they could be basically used in clinical targeted therapy.

Acute Toxicity of Oxyclozanide Suspension in Mice by Oral Administration

The safety of oxyclozanidc suspension was preliminarily evaluated through acute toxicity test in mice. Administration dose, formal trial grouping and group interval were determined in pre-trial using incremental method. Formal test was performed using simplified karber＇s method. Changes in sign of mice after ad- ministration were observed; the mortality rate was statistically calculated, and the time of death was recorded; the median lethal dose （LD50） and 95% confidence limit of oxyclozanide suspension were calculated. The results showed the LD50 of oxyclozanide suspension in mice by oral administration was 1. 679 g/kg, and the 95% confidence interval was 1. 439 - 1. 947 g/kg. According to toxicity grading of chemicals, oxyclozanide suspension was low toxic substance.

Acute Oral Toxicity Studies of a Chinese Herbal Preparation Shenrong Bunao Capsule

[ Objectives] This study was conducted to evaluate the acute oral toxicity of Shenrong Bunao Capsule, and to provide a theoretical basis for drug devel- opmcn! and clinical trims. [ Methods] Kunming mice were randomly assigned into two groups： an experimental group and a control group. In experimental group, Shenrong Bunao Capsule solution at maximum concentration of 45% was administered orally by gavage once at a dose of 30 ml/kg body weight （ BW）, while an equal volume of saline solution was given in the control group. Then, the appearance, behavior, mental state, diet, feces, urine, coat, skin color, respiration, nose, eyes and oral secretions and other daily activities of the mice were observed for 14 d after drug administration. At the end of the experiment, the mice were dissected, and their main organs were examined histopathologically. [Results] The appearance, behavior, respiration, body posture, response to stimuli and weight gain of the mice in control group were all normal. All the mice given 13. 500 g/kg BW Shenrong Bunao Capsule were alive 14 d after drug administration, and their appearance, behavior, respiration, body posture, response to stimuli and weight gains did not show any abnormality. In addition, the body weights of male and female mice had no obvious difference between the experimental group and the control group at the binging, 7 and 14 d after drug administration （P 〈0.05）. [ Conclusions] A maximum dose 13. 500 g/kg BW Shenrong Bunao Capsule, which was equivalent to 141 times of the recommended dosage for adult men was given to the mice, and did not result in any apparent toxic effects, suggesting that the Chines herbal preparation Shenrong Bunao Capsule has very little acute toxicity, and the commonly recommended dosage in clinical trials is safe.

Separation of Molds in Contaminated Fruits and Toxicity Test

[Objectives]This study was conducted to investigate the toxicity of molds in contaminative fruits.[Methods]Common fruits were used as materials to isolate contamination molds and screen the most virulent strain to study its pathogenic mechanism.[Results]We isolated eight kinds of strains from red bayberries,pears,oranges and peaches,and the P2 strain from red bayberries was the most virulent strain,which was preliminarily identified as Aspergillus luchuensis.The toxin from the strain led to the bone marrow cell micronucleus phenomenon,and the greater the toxin dose,the greater the micronucleus rate.With the extension of time,the micronucleus rate increased.The SOD activity of the kidney was inhibited after the mice were exposed to the toxin,and the greater the toxin dose,the lower the SOD activity.With the extension of time,the SOD activity decreased,but increased instead after 48 h because the toxin was metabolized in the body.It was always lower than that of control group.The MDA content in kidney was also affected after the exposure,and the greater the toxin dose,the higher the MDA content.Specifically,it increased with the time prolonged and began to decrease until 48 h,but not less than the control group.It indicated mold contamination in fruits produced toxins,and the P2 strain was the most toxic in red bayberries,causing chromosome and kidney injury.[Conclusions]This study provides a theoretical basis for the isolation and identification of molds in different fruits and toxicity tests,which is helpful to enhance people’s understanding of mycotoxins and their harm.

Estimation of cytotoxic potency by brine shrimp lethality bioassay application of Clerodendrum infortunatum Linn.

Objective:To learn a scientific and systematic knowledge of anticancer,antimicrobial and pharmacological activities of natural products and estimate cytotoxic potency by using ethanol and chloroform extracts of root,leaf and stem of Clerodendrum infortunatum(Verbenaceae)due to its random use in customary and traditional medicine to cure common ailments such as intestinal disorder,diarrhea,tuberculosis and respiratory problems etc.Methods:The in vitro application was carried out with the bench-top bioassay method by using brine shrimp lethality bioassay.Results:All of the crude extracts were found to be lethal and effective.The LC50 value of ethyl alcohol fraction of root was 20.845 mg/L compared to the standard drug tetracycline of 14.675 mg/L to brine shrimp nauplii,indicating that the extracts were biologically active.Conclusions:The cytotoxic study of LC50 value showed that a good correlation with the antibiotic tetracycline.From the comparative correlation error bars and percentage,we understood that ethyl alcohol fraction of root extract was very effective.This study serves as a basis for further research to lead compounds to be isolated so that it may be as a template for the implications of these results for bioactivity and drug discovery potential of herbal products.

Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats

Litsea elliptica Blume has been traditionally used to treat headache,fever,and stomach ulcer,and has also been used as an insect repellent.The acute and subacute toxicities of L.elliptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats.For the acute toxicity study,L.elliptica essential oil was administered in doses from 500 to 4 000 mg/kg(single dose),and in the subacute toxicity test,the following doses were used:125,250,and 500 mg/kg,for 28 consecutive days.In the acute toxicity study,L.elliptica essential oil caused dose-dependent adverse behaviours and mortality.The median lethal dose value was 3 488.86 mg/kg and the acute non-observed-adversed-effect level value was found to be 500 mg/kg.The subacute toxicity study of L.elliptica essential oil did not reveal alterations in body weight,and food and water consumptions.The haematological and biochemical analyses did not show significant differences between control and treated groups in most of the parameters examined,except for the hemoglobin,mean cell hemoglobin concentration,mean cell volume,mean cell hemoglobin,serum albumin,and serum sodium.However,these differences were still within the normal range.No abnormalities or histopathological changes were observed in the liver,pancreatic islet of Langerhans,and renal glomerulous and tubular cells of all treated groups.In conclusion,L.elliptica essential oil can be classified in the U group,which is defined as a group unlikely to present an acute hazard according to World Health Organization(WHO) classification.

Article Preclinical evaluation of acute systemic toxicity of magnesium incorporated poly(lactic-co-glycolic acid)porous scaffolds by three-dimensional printing Jing

Biodegradable polymer scaffolds combined with bioactive components which accelerate osteogenesis and angiogenesis have promise for use in clinical bone defect repair.The preclinical acute toxicity evaluation is an essential assay of implantable biomaterials to assess the biosafety for accelerating clinical translation.We have successfully developed magnesium(Mg)particles and beta-tricalcium phosphate(β-TCP)for incorporation into poly(lactic-co-glycolic acid)(PLGA)porous composite scaffolds(PTM)using low-temperature rapid prototyping three-dimensional-printing technology.The PTM scaffolds have been fully evaluated and found to exhibit excellent osteogenic capacity for bone defect repair.The preclinical evaluation of acute systemic toxicities is essential and important for development of porous scaffolds to facilitate their clinical translation.In this study,acute systemic toxicity of the PTM scaffolds was evaluated in mice by intraperitoneal injection of the extract solutions of the scaffolds.PTM composite scaffolds with different Mg andβ-TCP content(denoted as PT5M,PT10M,and PT15M)were extracted with different tissue culture media,including normal saline,phosphate-buffered saline,and serum-free minimum essential medium,to create the extract solutions.The evaluation was carried out following the National Standard.The acute toxicity was fully evaluated through the collection of extensive data,including serum/organs ion concentration,fluorescence staining,and in vivo median lethal dose measurement.Mg in major organs(heart,liver,and lung),and Mg ion concentrations in serum of mice,after intraperitoneal injection of the extract solutions,were measured and showed that the extract solutions of PT15M caused significant elevation of serum Mg ion concentrations,which exceeded the safety threshold and led to the death of the mice.In contrast,the extract solutions of PT5M and PT10M scaffolds did not cause the death of the injected mice.The median lethal dose of Mg ions in vivo for mice was determined for the first time in this study to be 110.66 mg/kg,and the safety level of serum magnesium toxicity in mice is 5.4 mM,while the calcium serum safety level is determined as 3.4 mM.The study was approved by the Animal Care and Use Committee of Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences(approval No.SIAT-IRB-170401-YGS-LYX-A0346)on April 5,2017.All these results showed that the Mg ion concentration of intraperitoneally-injected extract solutions was a determinant of mouse survival,and a high Mg ion concentration(more than 240 mM)was the pivotal factor contributing to the death of the mice,while changes in pH value showed a negligible effect.The comprehensive acute systemic toxicity evaluation for PTM porous composite scaffolds in this study provided a reference to guide the design and optimization of this composite scaffold and the results demonstrated the preclinical safety of the as-fabricated PTM scaffold with appropriate Mg content,strongly supporting the official registration process of the PTM scaffold as a medical device for clinical translation.