The lung is one of the important target organs of chemical poisoning. Chemical toxins may be absorbed into body through blood circulation of the lungs,inducing systemic damage. Mean?while,they may also directly damage the lungs themselves. Lung injury is usually rapid and life-threatening. This review systematically introduced the toxicological mechanisms and poisoning management of lung injury agents.

The number of chemicals that are synthesized each year has been steadily increasing. Chemicals are of immense benefits to mankind,many of which,however,have a significant negative impact on the environment as well as human health primarily due to their inherent chemistry and toxici?ty. Human exposure to numerous toxic chemicals takes place not only in the environment and but also in the workplace. Therefore,new approaches to toxicology need to developed. A milestone in this regard is the versions of the US National Research Council ″Toxicity Testing in the 21st Century:a Vision and a Strategy ″ and ″Science and Decisions:Advancing Risk Assessment ″. The versions require a radical paradigm shift in the approach to safety assessment and in the traditional procedure where animal experiments used to be the dominating technology. The future of toxicology suggests a new conceptual framework within which in vitro and in silico approaches based on human materials are used to under?stand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. This paper focuses on the many challenges and issues that need to be solved in this area.

Chemical warfare agents and chemical terrorism agents have been identified as one of the major threats to human survival and national security currently. The key to dealing with these threats is the effective medical countermeasures of which specific antidotes take center stage. In the past decade,real or potential chemical threats which has sparked regional conflicts,terrorist activities or chemical accidents intentionally or unintentionally have increased the investment in antidotes research and development worldwide. Here,we introduced the research status on medical countermeasures against chemical threat by giving an overview of the United States ″Countermeasures Against Chemi?cal Threats(CounterACT)Program″,and then the recent research progress in antidotes against nerve agents,sulfur mustard and cyanide toxicities were reviewed.

OBJECTIVE To evaluate the cardiotoxicity of a widen-spectrum antineoplastic drug, gambogic acid, through quantitative multiple cellular phenotypic characterization. METHODS H9c2 cell line was used as a model with doxorubicin (Dox) and amiodarone (Ami) as positive controls, hypaconi?tine as negative control and 0.1% DMSO as normal control. An optimized protocol was established to identify the morphology and function of cell nuclei. The effect of drugs on cell viability, nuclear area (Hoechst33342), mitochondria mass (MitoTracker Deep Red) and cytoplasmic calcium ion mobilization (Rhod2 AM)was studied. EC50 and Z′values were calculated to evaluate the degree of toxicology and to estimate the precision and false-positive rate, respectively. RESULTS Dose-response analysis indicated that EC50 of Dox on cell viability, nuclear area, mitochondrial mass was 0.72, 0.014 and 1.21μmol · L-1, respectively. On the other hand, EC50 of Ami on the parameters of cell viability, nuclear area and mitochon?drial mass was 14.83, 6.72 and 4.54μmol·L-1, respectively with Z′value above 0.5. Hypaconitine decreased the SER ridge of mitochondria. Gambogic acid caused significant mortality of H9c2 cells and induced nuclear shrinkage as Ami did. The EC50 values of cell viability and nuclear area were 0.24 and 1.16 μmol · L- 1. Meanwhile,gambogic acid disturbed the mitochondrial function as indicated by the increased mitochondrial area (EC50=0.44 μmol · L-1), abnormal SER Ridge(EC50=0.99 μmol · L-1) and decreased mitochondrial mass(EC50=1.21 μmol · L- 1). Cellular calcium mobilization was lower than normal (EC50=0.41 μmol · L-1). CONCLUSION The EC50 values of positive controls calculated from our assessment are similar those reported in literature. A multi-parameter and simultaneous evaluation enables a comprehensive analysis of the morphology of nuclei and mitochondria of cardiomyocytes and a preliminary assessment of the mechanisms of toxicity.

Conotoxins are secreted by Conus snail,which are mainly composed of 12-40 amino acid residues and several disulfide bridges. Their diversities in sequences,disulfide bond connections and modified amino acids are different from those of peptide toxins and proteins secreted by terrestrial animals,and their targets include sodium,potassium,calcium ion channels and membrane receptors. Conotoxins have been categorized into more than 20 superfamilies,such as A,M,O,P,S,T,I,V, Y,J,D,C and L,which are characterized by consensus signal sequences and cysteine framework. According to pharmacological functions,these superfamilies are further classified into several pharma?cological families,such as α,μ,ω,κ,δ,ψ,σ,ρ,γ,conopressin and conantokins. This review briefly introduced the classifications and diversities of conotoxins,and summarized the progresses in the toxi?cology and pharmacology of conotoxins targeting calcium,sodium ion channel,nicotinic acetylcholine receptor and N-methyl-D-aspartic acid receptor. Some of the above conotoxins are highly poisonous,some have been developed as drugs or drug candidates,or have become powerful research tools for neuro?pharmacology. We hope this review will contribute to researches of toxins and related neuropharmacology.

OBJECTIVE To observe the effect of baicalin on Aβ25-35 induced learning and memory deficits and changes in autophagy-related genes in mice so as to explore the related mechanisms of Alzheimer disease (AD) treatment . METHODS C57 mice were administered with 3μL Aβ25-35 3 mmol·L-1 by intracerebroventricular injection to establish an AD model. Baicalin was given by intracerebroventricular injection at the dose of 25, 50 and 100 mg · kg-1 for 15 d, respectively. The total distance and the central grid residence time were measured in the open-field test. The escape latency and the time to reach the platform were monitored in the Morris water maze trial. The autophagic vacuoles in the hippocampus of the mice were observed by transmission electron microscopy before the protein expressions of microtu?bule-associated protein 1 light chain 3 (LC3) and Beclin1 in brain tissue were analyzed by Western blot?ting assay. RESULTS Intracerebroventricular injection of Aβ25-35 could reduce the total distance from (3984±321)cm to (2790±306)cm and extend central grid residence time from (3.6±1.2)s to (8.8±2.9)s in the open-field test. The escape latency of water maze also increased from (22.0 ± 1.9)s to (38.8 ± 2.2)s. Autophagic vacuoles or late autophagic vacuoles and increased Beclin1 and LC3 and protein level were observed in the hippocampus after Aβ25-35 injection. Intraperitoneal injection of Baicalin 50 and 100 mg · kg-1 for fifteen consecutive days extended the total distance in open-field test to (3705 ± 337)cm and (3968 ± 448)cm, respectively, while the central grid residence time was reduced to (5.6 ± 1.8)s and (3.9±1.5)s, respectively. The total time taken to reach the platform in water maze test was reduced to (28.6± 1.9)s, (22.9 ± 1.7)s. Mitochondrial swelling, vacuolar membrane structure or autophagic vacuoles were visible in the hippocampus. LC3 and Beclin1 protein expression was significantly up-regulated(P<0.01). CONCLUSION Baicalin shows protective effect against Aβ25-35 induced learning and memory deficits, and this effect may be related to the activation of autophagy in the mouse hippocampus.

Ricin is a plant toxin isolated from the seed of the castor plant(Ricinus communis). As a typical II ribosome inactivating protein,ricin consists of two polypeptide chains named ricin toxin A chain(RTA)and ricin toxin B chain(RTB),linked via a disulfide bridge. RTB binds to both glycopro?tein and glycolipid at the surface of the target cell and mediates ricin to be endocytosed and transported retro?gradely to the endoplasmic reticulum. After being reduced and retrotranslocated to the cytosol,RTA mediates its toxicity due to its activity of a RNA N- glycosidases. Aside from its main toxic effect of protein synthesis inhibition,ricin also displays other properties that contribute to its toxicity such as inducing apoptosis,cytokine secreting and peroxidation. Ricin is stable and can be easily isolated. It has many routes of intoxication with no specific antidotes. Due to its natural abundance,remarkable toxicity,and the potential to be used in biological warfare as well as terrorist attacks,ricin has been classified as a Category B biothreat agent. Here we reviewed its history as a biothreat agent,constitu?tion,intoxication mechanism,detection methods and the development of specific antitodes.

The lung is a major damage tissue in paraquat(PQ)-caused acute poisoned patients. Most deaths from acute PQ poisoning can be attributed to acute lung injury(ALI). Complement activa?tion product C5a causes inflammatory cells,such as neutrophils and macrophages,to accumulate into the lung and get activated. These activated inflammatory factors generate a large number of oxidants and inflammatory sequelae named cytokine storm to mediate ALI induced by PQ poison. The review focused on the role and mechanisms of complement C5a in PQ-induced ALI.

OBJECTIVE To investigate the effect of overexpession of 18 ku translocator protein (TSPO) on the hippocampal dentate gyrus. METHODS Lentiviral (LV) vectors containing TSPO or the lentiviral sequence were infused into the hippocampus bilateral dentate gyri (2 × 108 TU · mL-1,1 μL per side)of mice. Behavioral tests were carried out. The anxiolytic-like behavior of mice was examined by such means as the elevated plus maze test , the staircase test , light dark box test for 12, 14 and 16 d, two behavioral despair models, tail suspension test and the forced swimming test for 16 and 18 d,respec?tively. Western blotting and ELISA were used to evaluate the TSPO expression and the concentration of allopregnanolone in hippocampal tissue (3 mm in diameter around the injection site on both sides) at the end of tests. RESULTS The results of behavioral experiments showed that TSPO overexpression group deneloped anxiolytic and antidepression-like behavior. LV-TSPO significantly increased the retention time in the central area〔14 ± 4 vs (25 ± 12)s,P<0.05〕. LV-TSPO significantly increased the percentage of entry into open arms entries percentage and the percentage of time spent in open arms time without changing total entries and total time in the elevated plus-maze test〔(13±8)%vs (26±18)%, P<0.05;(6 ± 6)%vs (27 ± 6)%, P<0.05)〕. LV-TSPO significantly decreased the number of rearings without changing the number of steps in staircase test (21±7 vs 12±5,P<0.05). LV-TSPO increased entries into the light area and retention time in light-dark transition test〔(18 ± 8)% vs (26 ± 7)%, P<0.05;72 ± 36 vs (191 ± 90)s, P<0.05)〕but significantly decreased immobility time in the tail suspension test and forced swimming test〔94±33 vs (36±20)s, P<0.01;137±36 vs (90±37)s, P<0.05)〕, without excitatory or inhibitory actions on the central nervous system. At the same time, the level of TSPO expression in hippocampal tissues (3 mm in diameter around the injection site on both sides) was significantly increased, so did the concentration of allopregnanolone (P<0.05). CONCLUSION Overexpression of TSPO in the hippocamus dentate gyrus of mice can induce anxiolytic and antidepressant-like behavior, and the downstream allo?pregnanolone biosynthesis at least partially mediates the behavioral effects.

Mycotoxins,secondary metabolites produced by certain fungi,have become one of the most harmful factors that affect the clinical safety of medicinal herbs that probably can be contaminated by harmful toxins generated from fungi in the whole process from planting to clinical use. Therefore,more toxicological research of mycotoxins,a better knowledge of the pathogenesis and quick detection with sensitivity and accuracy will play an important role in targeted therapy of poisoning by mycotoxins and early warning . In this paper,the current status of mycotoxin contamination in medicinal herbs was ana?lyzed,and the progress of toxicological study on common contaminants was reviewed. In view of the high toxicity of toxins,the strategy of ″Prevention First″ is highly desirable. Hence,the development of rapid detection of typical mycotoxins was systematically discussed. The review was intended to provide ref?erence for ensuring clinical safe administration of medicinal herbs and for reducing the risk of mycotoxin poisoning.