Acute Toxicity of Jinchuan Formula Plum Wine Extract and Its Protective Effect on Mice with Liver Injury

[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.

Histological Assessment and Transcriptome Analysis Provide Insights into the Toxic Effects of Perfluorooctanoic Acid to Juvenile Half Smooth Tongue Sole Cynoglossus semilaevis

Perfluorooctanoic acid(PFOA)is a widespread synthetic persistent organic pollutant that may enrich along the food chain and affect the growth,development,reproduction,and lipid metabolism of aquatic organisms,particularly the benthic organisms.How-ever,the toxic effects of PFOA on the half-smooth tongue sole Cynoglossus semilaevis,a commercial benthic fish in China,have rarely been reported.Because juvenile fish are sensitive to environmental pollutants,in the present study,histological assessment and tran-scriptome sequencing were performed to determine the short-term impact of PFOA on juvenile half-smooth tongue soles.Histologi-cal analysis showed that PFOA exposure caused hepatocyte rupture,intestinal villi breakage,increased goblet cell count,and brain ab-normal.Transcriptome results showed that some interesting signaling pathways,such as glycolysis/gluconeogenesis,PPAR signaling pathway and GABAergic synapse signaling pathway,were enriched after PFOA exposure.In addition,some metabolic,immune and neural genes were differentially expressed,which including ependymin,hbb1-like and gad 1,and they were up-regulated after 14 days of exposure.Transcriptome results also indicated that half-smooth tongue sole might improve energy metabolism in response to PFOA toxicity after 7 days of exposure.These findings provide a basis for studying the ecological effects of PFOA on marine benthic fishes.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis

Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies.As this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes paramount.IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications.However,a precise picture of IMC pathophysiology is currently unavailable.Therefore,we aimed to summarize the existing data while acknowledging the need for further research.This comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and features.Our review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of colitis.Furthermore,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.

Toxic Effects of Lanthanum, Cerium, Chromium and Zinc on Potamogeton Malaianus

The toxic effects of rare earth elements such as lanthanum, cerium and heavy metal elements such as chromium, zinc on Potamogeton malaianus Miq. were studied. The results show that the contents of chlorophyll and soluble protein increase to a certain degree and then decrease under La3+ Ce3+ Zn2+ stress, while there is a constantly dropping tendency under Cr6+ stress. The four ions have different effects on protective enzyme systems of Potamogeton malaianus. They can induce rises of the activities of catalase (CAT) and peroxides (POD) at lower concentration, however, with the increase of ions concentration, the activities decline. The change of SOD activity is exactly opposite to that of CAT and POD activity. It falls at first and rises later. An increasing tendency of MDA content appears with the increasing concentration. The toxicities of La3+, Zn2+, Ce3+ and Cr6+ become more serious in the order. The lethal concentration of Cr6+ to Potamogeton malaianus ranges from 0.5 to I mg(-1) that of Ce3+ and Zn2+ ranges from 3 to 5 mg(-1) and that of La3+ ranges from 7 to 10 mg(.)L(-1). The toxic mechanism of La3 + and Ce3+ is similar to that of Cr6+ and Zn2+.

Toxic effects of acetochlor, methamidophos and their combination on nifH gene in soil

Toxic effects of two agrochemicals on nifH gene in agricultural black soil were investigated using denaturing gradient gel electrophoresis （DGGE） and sequencing approaches in a microcosm experiment. Changes of soil nifH gene diversity and composition were examined following the application of acetochlor, methamidophos and their combination. Acetochlor reduced the nifH gene diversity （both in gene richness and diversity index values） and caused changes in the nifH gene composition. The effects of acetochlor on nifH gene were strengthened as the concentration of acetochlor increased. Cluster analysis of DGGE banding patterns showed that nifH gene composition which had been affected by low concentration of acetochlor （50 mg/kg） recovered firstly. Methamidophos reduced nifH gene richness that except at 4 weeks. The medium concentration of methamidophos （150 mg/kg） caused the most apparent changes in nifH gene diversity at the first week while the high concentration of methamidophos （250 mg/kg） produced prominent effects on nifH gene diversity in the following weeks. Cluster analysis showed that minimal changes of nifH gene composition were found at 1 week and maximal changes at 4 weeks. Toxic effects of acetochlor and methamidophos combination on nifH gene were also apparent. Different nifH genes （bands） responded differently to the impact of agrochemicals： four individual bands were eliminated by the application of the agrochemicals, five bands became predominant by the stimulation of the agrochemicals, and four bands showed strong resistance to the influence of the agrochemicals. Fifteen prominent bands were partially sequenced, yielding 15 different nifH sequences, which were used for phylogenetic reconstructions. All sequences were affiliated with the alpha- and beta-proteobacteria, showing higher similarity to eight different diazotrophic genera.

TOXIC EFFECTS OF Zn^(2+), Cu^(2+), Cd^(2+)and NH_3 ON CfflNESE PRAWN

This study deals with the toxic effects of Zn2+, Cu2+, Cd2+ and NH3 on Chinese prawn (Penaeus orientalis). The median lethal concentrations of the toxic matters on Chinese prawn were determined. Cd2+】Cu2+】Zn2+】NH3-Nm is the toxic order of these chemicals to Chinese prawn. The toxic order of concentrated Zn2+ and Cd2+ in tissues and organs of Chinese prawn is in the order gill 】 shell + appendage】viscera 】 muscle..

Monitoring bioaccumulation and toxic effects of hexachlorobenzene using the polyurethane foam unit method in the microbial communities of the Fuhe River,Wuhan

Hexachlorobenzene （HCB） is a chlorinated aromatic hydrocarbon that was widely used for seed dressing in prevention of fungal growth on crops, and also as a component of fireworks, ammunition, and synthetic rubbers. Because of its resistance to degradation and mobility, HCB is widely distributed throughout the environment and is accumulated through food chains in different ecosystems. In this study, a preliminary investigation was carried out on the bioaccumulation and the toxic effects of HCB in the microbial （protozoan in particular） communities in the Fuhe River, Wuhan, a water body receiving industrial wastewaters containing HCB and other pollutants, using the standardized polyurethane foam units （PFU） method. Field samples were taken from eight stations established along the Fuhe River in January and August 2006. The concentration ratios of HCB in microbial communities and in water were 9.66-18.64, and the microbial communities accumulated 13.29-56.88 μg/L of HCB in January and 0.82-10.25 μg/L HCB in August. Correlation analysis showed a negative correlation between the HCB contents in the microbial assemblage, and the number of species and the diversity index of the protozoan communities. This study demonstrated the applicability of the PFU method in monitoring the effects of HCB on the level of microbial communities.

Toxic Effects of Nano-CuO, Micro-CuO and Cu²⁺on <i>Chlorella</i>sp.

The 96 h acute toxic effects of nano-CuO (N-CuO), micro-CuO (M-CuO) and 2+ on Chlorella sp. were investigated in this paper. The results showed that toxicities decreased in an order of Cu2+>N-CuO>M-CuO. The 96 h EC50 of Cu2+ on Chlorella sp. was 1.06 mg /L, and of N-CuO it was 74.61 mg /L, while no pronounced toxicity was observed when the concentration of M-CuO was lower than 160 mg/L. Further experiments were carried out in order to study the toxicity mechanism of nano-CuO on Chlorella sp.. The results of Cu2+ release from N-CuO showed less than 0.2 mg/L Cu2+ were released, so the release of Cu2+ was not responsible for the toxicity. Further experiments showed N-CuO inhibited formation of Chlorophyll A. Content of Chlorophyll A in the control group was 4.75 mg/108 cells, while it declined to 2.89 mg/108 cells for 160 mg/L N-CuO after 96 h, which indicated that N-CuO could inhibit photosynthesis of Chlorella sp.. Moreover, N-CuO condensed with algal cells. It affected the activity of SOD and POD, indicating that N-CuO could cause oxidant stress to Chlorella sp.. These may be the toxicity mechanism.

Toxicity Evaluation of in vitro Cultures of Freshwater Cyanobacterium Microcystis aeruginosa:Ⅰ.Hepatotoxic and Histopathological Effects in Rats

Laboratory cultures of freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa PCC 7806 was cvaluated for its hepatotoxic effects in rats. The lyophilized cell extract injected intraperitoneally at 1 and 2 LD50 (15.8 and 31.6 mg/kg, respectively) produced significant increase in liver-specific enzymes viz. plasma alkaline phosphatase,γ-glutamyl transferase, lactate dehydrogenase with a concomitant decrease in hepatic glutamic pyruvic transaminase. A corresponding increase in liver body weight index and histopathological changes in liver (degeneration of hepatocytes, congestion and hemorrhage etc.) are indicative of a dose and time dependent hepatotoxic nature of the algal extract

Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose

The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.

Influences of Chloropazine, Nimodipine and Their Combination on the Toxic Effects of Cadmium in Liver and Kidney of Mice

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

Exposure Level, Toxicity Effects and Health Risk Assessment of Organophosphorus Flame Retardants in Water Environment

Organophosphorus flame retardants(OPFRs) are gradually replacing brominated flame retardants(BFRs), which are widely used in the world. The increasing output of OPFRs and the increasing detection of OPFRs in environmental media have attracted wide attention of scholars at home and abroad. OPFRs are generally semi-volatile, easy to enter the environment and accumulate in organisms,causing potential hazards to the environment and human health. In this paper, the pollution status and toxic effects of OPFRs in aquatic environment were introduced,and the research progress of human health risk caused by them was summarized.The existing problems were pointed out, and the future research was prospected. In the future, the analytical methods of various environmental and biological media should be improved, and comprehensive and in-depth environmental investigation and ecological and health risk assessment should be carried out. Attention should be paid to the effects of combined pollution on organisms and the study of biological acceptability.

Evaluation of Acute Toxicity and Sedative Effects of Ethylic Extract of <i>Thymelaea lythroides</i>in Wistar Rats

The purpose of this study was to evaluate the acute toxicity and sedative effect of the ethylic extract of Thymelaea lythroides (Tl) on Wistar rats. The study was based on the gavage administration of the ethylic extract of Tl with different doses (i.e. 200, 400, 500 and 5000 mg/kg), where the toxicity and the sedative activity of the plant were observed and the obtained results were analyzed using the ANOVA test followed by the Bonferroni test. The main results of this study showed that the lethal dose of the ethylic extract of Tl was higher than the 5000 mg/kg dose. Moreover, when compared to the control rats, the animals treated with 5000 mg/kg of the extract exhibited significant reduction in appetite for food and water in the first week. Furthermore, results of the psychotropic test conducted during this study showed visible effects on the exploratory activity of the rats. The dose of 5000 mg/kg was also found to have a significant central nervous system effect;the locomotor activities of the animals decreased in a manner similar to those administered with Zepam as control.

Toxic Effects of Four Commonly-used Agrochemicals on Arma chinensis and Picromerus lewisi

This study was conducted to investigate the toxic effects of four different agrochemicals on Arma chinensis and Picromerus lewisi . Cypermethrin·phoxim, imidacloprid and fenvalerate had higher toxic effects on A. chinensis and P. lewisi . After the application of the agrochemicals, the released stink bugs could not well survive and propagate. Though the herbicide （glyphosate ammonium） had no direct toxic effects on A. chinensis and P. lewisi , their survival and propagation were affected after the application of the herbicide into natural environment. Therefore, to ensure better survival and propagation of the two kinds of stink bugs in natural environment, local agrochemical management should be strengthened, and the concept of green environmental protection should be constructed and popularized.

Protective Effects of Certain Natural and Synthetic Complexans on the Toxicity of Chromium and Tin to a N_2-Fixing Cyanobacterium, Anabaena doliolum

The effects of chromium and tin on survival, growth, carbon fixation, nitrate reduction, ammonia assimilation, and nitrogenase activity of a N_2-fixing cyanobacterium, Anabaena doliolum, and their amelioration by synthetic and natural complexans, viz., EDTA, nitrilotriacetic acid (NTA), pyridine dicarboxylic acid (PDA), and citrate, have been studied. Chromium proved to be much more toxic than tin, as it inhibited growth yield (49%), carbon fixation (53%), and nitrate reductase (79%), glutamine synthetase (30%), and nitrogenase activities (77%) at its sublethal concentration, whereas tin induced less inhibition of growth yield (42%), carbon fixation (50%). and nitrate reductase (66%), glutamine synthetase (32.4%), and nitrogenase activities (70%). Despite its inhibitory effects at 10μml^(-1), EDTA supplementation in metal-spiked medium counteracted the toxicity of chromium and tin more significantly than NTA, PDA, and citrate. When supplemented with LD_(50) of Cr, EDTA protected growth, carbon fixation, NR, GS. and Noase, respectively, by 32.6, 50.0, 33.3. 17.7. and 65.4%. However, EDTA-induced restoration of the above parameters at a sublethal concentration of tin was only 30.2, 50.0,28.1, 27.7, and 61.5%, respectively. Although NTA and citrate at 10/μgml^(-1) each were stimulatory to various processes of test cyanobacterium, they were comparatively less effective than EDTA in the amelioration of metal toxicity. On the basis of these observations, a generalized hierarchical sequence of protective efficiency of synthetic and natural cornplexing ligands may be given as EDTA > NTA > citrate > PDA. It seems plausible that the toxicity of various heavy metals may be regulated by a large array of organic complexing agents of the aquatic environment because they possess various metal binding sites. (c) 1989 Academic Press,lnc.

Acute Toxic Effects of Mercuric Chloride on the Mucocytes of the Epithelial Lining of the Accessory Respiratory Organ and Skin of the Air Breathing Catfish Heteropneustes fossilis（Bloch）^1

Acute toxicity of 0.3 ppm mercuric chloride on the mucocytes of the branchial diverticulum and skin of Heteropneustes fossilis results in cyclic increases followed by decreases in the density, area occupancy and volume at different intervals of exposure. The alterations in the two tissues do not follow the same path perhaps due to different modes of action of the mercury salt: The skin comes under direct contact effects, while the branchial diverticulum may be affected by hormonal imbalance caused by a stress effect.

Joint toxic effects of heavy metals and atrazine on invasive plant species Solidago Canadensis L.

In this study, the joint effects of Cd(Ⅱ), Pb(Ⅱ) and atrazine (ATR) on Solidago Canadensis L. were investigated. The results showed that soil containing Cd, Pb and ATR could inhibit root elongation of Solidago Canadensis L., and that there was a positive linear relationship between the inhibitory rate of root elongation and the concentrations of Pb(Ⅱ). The mixture of Cd(Ⅱ) and Pb(Ⅱ)-ATR in soil showed a significant adverse effect on root and shoot biomass of Solidago Canadensis L. Acetylsalicylic acid (ASA) contents increased slightly at the lower concentrations of Cd(Ⅱ)-ATR, then decreased when Cd(Ⅱ)-ATR concentrations were higher than those of 1.0 TUmix(Cd+ATR). The toxic effect of Pb(Ⅱ)-ATR on the ASA contents of Solidago Canadensis L. was greater than that of Cd(Ⅱ)-ATR. Soluble sugar contents firstly decreased and then increased with increasing concentrations of Cd(Ⅱ)-ATR and displayed fluctuation with increasing concentrations of Pb(Ⅱ)-ATR. Total protein contents in-creased with increasing concentrations of Cd(Ⅱ) and Pb(Ⅱ)-ATR , relative to the control sample. The NP-SH con-tents showed a significant increase up to 12.2 mg/gfw of Cd(Ⅱ)-ATR, followed by a significant decline to 4.5 mg/gfw after 14 days of exposure. The effect of Pb(Ⅱ)-ATR was similar to that of Cd(Ⅱ)-ATR but the amount of NP-SH was not higher than that of Cd(Ⅱ)-ATR.

Toxicity Effect of Hg^(2+) and Cr(VI) on Alga Growth in Eutrophic Water

[ Objective] The toxicity effect of Hg^2＋ and Cr（Ⅵ） on alga growth in eutrophic water was studied to provide reference for biomonitoring and bioremediation of eutrophic water. [ Method ] The mother liquid of alga, which was separated from the eutrophic water, were put into the solutions of Hg^2＋ and Cr（Ⅵ） with different concentrations and their mixture solution, respectively. And the toxicity effect of Hg^2＋ and Cr（Ⅵ） on the growth and propagation of alga in eutrophic water was observed. [ Result] The alga in eutrophic water performed rather sensitive to Cr（Ⅵ） and when its concentration was over 1 mg/L, threre was obvious effect on alga growth. The alga was not very sensitive to Hg^2＋ when its concentration was lower, but its toxicity became stronger and stronger when its concentration increased to some extent and the toxicity effect of Cr（Ⅵ） on alga growth was just on the contrary. When the ion concentration was lower than 10 mg/L, the toxicity of Hg^2＋ on alga was lower than that of Cr（Ⅵ）. When the concentration was over 10 mg/L, the toxicity of Hg^2＋ exceeded that of Cr（Ⅵ）. The toxicity of ion mixture solution of Hg^2＋ and Cr（Ⅵ） had synergism inhibition on alga, which could be performed only when the concentration was over 4 mg/L. [ Conclusion] The toxicity of heavy metal on alga not only related to the alga cell, but also related to the concentration of heavy metal ion.

Novel wine in an old bottle:Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound(‘old bottle’)as a novel drug(‘novel wine’)for the prevention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.