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.

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.

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.

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

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.

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.

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.

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..

Selectivity and sublethal effects of some frequently-used biopesticides on the predator Cyrtorhinus lividipennis Reuter(Hemiptera: Miridae)

The green miridbug,Cyrtorhinus lividipennis,is an important predator of the rice brown planthopper,Nilaparvata lugens.In this study,the selective toxicity of seven commercial biopesticides for C.lividipennis was examined under laboratory conditions; abamectin was the most selective to C.lividipennis,followed by matrine and azadirachtin.Veratridine,rotenone,Bacillus thuringiensis and Beauveria bassiana showed less selectivity for C.lividipennis.Subsequently,matrine,abamectin and azadirachtin were selected for sublethal assessments with respect to C.lividipennis due to their high toxicities to N.lugens.C.lividipennis treated with sublethal concentrations(LC10 and LC20) of the three biopesticides could distinguish volatiles released from healthy and N.lugens-infested plants indicating that the biopesticides tested did not affect the foraging ability of surviving miridbugs.Azadirachtin decreased the consumption capability of C.lividipennis when the densities of N.lugens were 20,30,40 and 50 insects per vial.Sublethal concentration treatment did not impact the pre-oviposition period or egg hatchability of C.lividipennis.However,the fecundity of C.lividipennis exposed to azadirachtin and abamectin increased by 27–41% compared to the untreated individuals.In summary,abamectin or matrine together with C.lividipennis could be considered an effective,sustainable pest management strategy for rice.

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.

Toxicity of perfluorononanoic acid and perfluorooctane sulfonate to Daphnia magna

In order to study toxicological effects of perfluorononanoic acid （PFNA）, perfluorooctane sulfonate （PFOS）, and their mixtures （PFNA/ PFOS） on Daphnia magna （D. magna）, a suite of comprehensive toxicity tests were conducted, including a 48-h acute toxicity test, a 21-day chronic test, a feeding experiment, and a biomarker assay. D. magna were exposed to aqueous solutions of PFNA and PFOS （alone and in combination） at concentrations ranging from 0.008 to 5 mg/L. The survival, growth, and reproduction of D. magna were monitored over a 21- day life cycle. The biomarkers, including acetylcholinesterase （ACHE）, superoxide dismutase （SOD）, and catalase （CAT） activities, were determined after seven days of exposure. PFOS was more toxic than PFNA based on the results of the acute toxicity test. Perfluorinated compounds （PFCs） inhibited both growth and reproduction of D. magna during the testing period. The ingestion rates and the biomarkers, including ACHE, SOD, and CAT activities, were significantly inhibited by PFCs in most cases. Moreover, the combined effects related to the growth and reproduction showed the antagonistic effects of PFCs.

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.

Investigation of the immune effects of Scutellaria baicalensis on blood leukocytes and selected organs of the chicken＇s lymphatic system

Background： The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its health and to find novel and sustainable solutions. This paper presents a study on investigation of the effect of Scutellaria baicalensis root（SBR） on the immune response of broiler chicken, especially on lymphocytes and heterophils reactivity, regarding their contribution to the development of immunity of the chickens.Methods： The 121-day-old Hubbard Hi-Y male broiler hybrids were randomly assigned to four treatment groups,three SBR supplemented groups（0.5, 1.0, and 1.5% of SBR） and one control group. Each treatment was replicated five times with six birds per replicate pen in a battery brooder. Blood was collected after 3-（rd） and 6-（th）wk of the experiment, and hemoglobin and hematocrit values were determined, as well as total leukocyte count and differential count were performed. Nitroblue tetrazolium test and phagocytosis assay as nonspecific immune parameters and humoral immune responses to the antigenic challenge by sheep red blood cells were performed.Moreover, the ability of peripheral blood lymphocytes to form radial segmentation（RS） of their nuclei was analyzed.Body weight and relative weight of spleen, liver, and bursa of Fabricius were recorded.Results： Results showed that mean heterophile/lymphocyte ratio increased in the SBR groups compared to the control group and the blood of the chickens showed lymphocytic depletion. The results also demonstrated that the relative weight of bursa of Fabricius and spleen in groups fed with SBR significantly decreased compared to the control group. This study also showed that the addition of SBR significantly inhibited the formation of RS of nuclei compared to some cytotoxic substances.Conclusion： We found that SBR supplementation should be carefully evaluated when given to poultry. The excess intake of SBR supplementation may cause immunologic inhibition and may negatively affect the development of immune organs. SBR has inhibited the formation of radial segmentation nuclei showing antimetastatic properties and also the phagocytosis of chicken heterophils.

Protective Effects of Calcium Antagonists on Cadmium-induced Toxicity in Rats

Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0. 44mg Cd/kg,ip), CPZ (5mg/kg, ip) or NIMO (8mg/kg, po) were administered every day to Sprague-Dawley (S. D. ) rats for a week. Then, urinary N- acetyl-β-D- glucosaminidase (NAG ), uri -nary cadmium and bloocl cadmium were measured. The accumulation of cadmium in the kid-ney cortex, content of renal calmodulin, hemoglobin and the ultrastructural damage of proxi-mal convoluted tubules of rats were examined three weeks after the last administration. Re-sults indicated that the calcium antagonists partly protected against toxic effects induced bycadmium in different manners. These data provide further evidence for the new hypothesisthat the cross effect of cadmium and calcium in calmodulin regulated systems may be responsi-ble for the mechanism of cadmium intoxication. 'The results suggested that the calcium antag-onists could be a new and promising approach in the therapy of heavy metaLinduced diseases

Testing Toxicity and Antidote Effect of Selenium Nanoparticles with <i>Paramecium caudatum</i>

A simple method for assessment of the toxicity and antidote effect of selenium nanoparticles with Paramecium caudatum is presented. Light microscopy in combination with computerized video tracking is employed for the determination of the survival time of P. caudatum. Up to 800 mg/L, selenium nanoparticles are not acutely toxic. With respect to a potential antidote effect, the lethality of silver nanoparticles, silver nitrate, sodium hydrogen selenite, and sodium selenite to P. caudatum was decreased and survival time was extended upon pre-treatment with selenium nanoparticles. Taken together, these findings suggest that administration of selenium nanoparticles attenuates exposure to toxicants. Selenium nanoparticles could be a good functional additive for food management in animals.

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.