Mean Lethal Dose Research Articles

ТОКСИКОЛОГИЧЕСКАЯ ОЦЕНКА ПРЕПАРАТА СУБМАСТИН-КРС В ОСТРОМ ОПЫТЕ НА ЛАБОРАТОРНЫХ ЖИВОТНЫХ

The article presents the results of toxicometric assessment of Submastin-KRS in an acute experiment on white laboratory rats and mice when it is intragastrically and intramuscularly administered. The preparation was administered once into the stomach using a metal atraumatic probe at a dose range from 2000,0 to 27 mg/kg. A single injection volume was 500,0 ml (mouse) and 0,5 ml (rat); intramuscularly – at doses from 5,0 to 1200,0 mg/kg in a volume of 21 ml per mouse and 250,0 ml per rat. The animals of the Placebo group, administered the preparation in the same volume and by the same method of administration, received sterile isotonic sodium chloride solution. It was found that in case of the tested methods of administration in the range of the studied doses of the preparation, there was no deaths of animals, therefore, the mean lethal dose (LD0,25) of the preparation Submastin-KRS was not determined. Consequently, the experimental data obtained make it possible to classify the dosage form of the preparation Submastin-KRS to low-hazard substances.

Determination of lethal (LD) and growth reduction (GR)doses on acute and chronic gamma- irradiated Bambara groundnut [Vigna subterranea (L.) Verdc.]varieties

ABSTRACT Bambara groundnut is a highly nutritious underutilized legume with enormous potential to sustain food security in resource-poor countries. However, its potential for improvement through conventional breeding (< 2% success rate) limitation due to the nature of the flowers. Thus, the most viable method of improving this crop is by creating genetic variability through induced mutagenesis. The present study was conducted to evaluate the radiosensitivity of two Bambara groundnut varieties irradiated with acute and chronic gamma irradiations to determine the lethal dose (LD) and growth reduction dose (GR). Healthy seeds of both varieties were exposed to acute gamma irradiation using Cesium-137 at 0, 25, 50, 75, 100, 125, 150, 175, 200, 250, and 300 Gy. For chronic irradiation, two-week-old seedlings of the two genotypes were exposed to accumulated doses of 0, 8.52, 17.04, 35.56, 34.09, 42.61, 59.65, 93.74, 144.87, 255.64, and 570.94 Gy, respectively, in Gamma Green House (GGH) for 60 days. The result from the variance analysis indicated highly significant differences (P < 0.01) for all evaluated traits except for internode length. A linear regression model was developed to determine the mean LD and GR of both genotypes. The established lethal doses (LD25, 50, 75) for acute gamma irradiation on Ex-Sokoto variety were 75, 160, and 250 Gy while 68, 148, and 227 Gy were recorded for Karo variety, respectively. For chronic irradiation, the established growth reduction doses for Ex-Sokoto were 47, 250, and 444 Gy, whereas 70, 264, and 452 Gy were observed in Karo. Variations were observed between the gamma-irradiated genotypes and the methods of irradiations. Generally, the growth, development, and survival rate of Bambara groundnut increase with a decrease in gamma-irradiation doses. The established LD and GR doses from this study can be utilized in large-scale mutagenesis breeding programs for generating a wide range of mutants in Bambara groundnut.

Acute and Subchronic Toxicity Studies of Combretum collinum Methanol Root Extract in Albino Rats

Combretum collinum root extract has been recognized long ago as traditional medicinal plant in curing several diseases among the indigenous people of Alela-land (Zuru), Kebbi State, Nigeria. This research work was carried out to evaluate the toxicological effects of Combretum collinum methanol root extract (CCME) in albino rats. Acute toxicity was performed by a fixed single oral administration at a dose of 10, 100, 1000 mg/Kg and 1600, 2900, 5000 mg/Kg. Subchronic toxicity studies of CCME was conducted at doses of 32, 63, 126 and 253 mg/Kg for 28 days. The result showed that acute administration of CCME resulted at mortality and general behavioral changes at 1000 to 5000 mg/Kg. Therefore, the estimated lethal dose (LD50) of CCME was 316.23 mg/Kg. Subchronic oral administration of CCME revealed a significant (P&lt;0.01) decrease in body weight in rats receiving 63 to 253 mg/Kg throughout the study period compared with the control group. The results also showed a significant (P&lt;0.01) increase in serum ALT, AST, creatinine, potassium and bicarbonate in rats administered with 126 and 253 mg/Kg of the extract. Haematological analysis of the same extract revealed a significant (P&lt;0.01) increase in WBC, HCT, MCV, MCH, MCHC, PLT, LYM and NEUT in rats receiving 126 and 253 mg/Kg only. Histopathological examination of liver revealed severe periportal inflammation, hypertrophy, areas of hydropic changes, cancerous tumor, areas of infiltration and necrosis of the hepatic cells while the kidney showed a mild mesengial hyperplasia, compressed blood vessels, glomerular degeneration, tubular degeneration and tubular widened lumen in rats treated with 63 to 253 mg/Kg. Therefore, caution should be applied as C. collinum root extract has a low mean lethal dose and would be toxic at higher concentrations.

Acinetobacter venetianus, a potential pathogen of red leg disease in freshwater-cultured whiteleg shrimp Penaeus vannamei

The genus Acinetobacter has recently emerged as bacterial pathogens associated with mass mortalities in aquaculture. Yet scarce information is available on Acinetobacter venetianus as a potential pathogen of whiteleg shrimp Penaeus vannamei. In the present study, an A. venetianus pathogen (SHF1) was confirmed as a causative agent of red leg disease in freshwater-cultured whiteleg shrimp. It showed a mean lethal dose (LD50) value of 3.8 × 105 CFU mL−1 and developed multiple resistances to phenicols, quinolones and tetracycline drugs used in aquaculture. In addition, the pathogenic A. venetianus could be effectively controlled by Bdellovibrio powder at 0.8 mg L−1, which exhibited significant antibacterial effect and displayed good protection against A. venetianus challenge in P. vannamei for six days. As far as we know, this is the first study to identify A. venetianus as a potential bacterial pathogen of red leg disease in freshwater-farmed whiteleg shrimp.

Chemical exposure hazardous for fish Hyphessobrycon eques through the incorrect release of oil in Amazon region

Incorrect discard of oil used by fishing ship in the brazilian north region has become a common activity. Despite the possible hazard to the aquatic organisms, still missing scientific data about their toxicity. Thus, this study aimed to evaluate the stress and lethality caused by lubricant oil (FSAOLU) on fish Hyphessobrycon eques. Therefore, it was used six different concentration diluted in water (0, 22, 24, 26, 28, 30 and 32% of oil) and three replaces during 96 hours. At the end or during the experiment (with dying fish), it was collected blood samples (cutting the caudal fin) to determine physiological changes. The FSAOLU showed mean lethal dose (LD50-96h) of 27.36%, classified as toxic causing alterations in glucose values from the 26%. The greater dilution of FSAOLU (32%) increased 115% in glucose values when compared to the control. Thus, lubricant oil when discarded in water, it present hazard to the aquatic organisms causing stress and mortality for fish being necessary adequate management to discard of this residue.

Neutralization of the lethal activity from Bothrops atrox venom by hyperimune llama serum (Lama glama).

To evaluate the capacity of the hyperimmune llama serum (Lama glama) to neutralize the lethal activity of Bothrops atrox venom in laboratory mice. Mean lethal dose (LD50) was calculated from a Bothrops atrox venom sample pool from Peru. The antibody titers were measured by ELISA assay; and the immune serum neutralization potency was measured by calculating the mean effective dose (ED50) during the immunization period. The venom's LD50 was 3.96 μg/g; similar to what was found in other studies about Bothrops atrox carried out in Peru. The titers of antibodies against the venom increased rapidly in the llama, demonstrating a fast immune response; however, the neutralization capacity increased slowly and required several doses and immunization reinforcements, obtaining a ED50 of 3.30 μL/g mouse and a neutralization potency of 3.6 mg/mL after 15 immunizations. The hyperimmune llama serum is able to neutralize the lethality of the Bothrops atrox venom from Peru in laboratory mice.

Evaluation of the Analgesic, Anti‐Cataleptic, Muscle Relaxant and Sedative Potential of The Ethanol Extract of Lophira alata Stem bark in Rodents

BackgroundLophira alata, a woody plant found in West and Central Africa is used in the treatment of several systemic disorders. This study was carried out to evaluate some neurobehavioural properties of Lophira alata in murine models of algesia, sedation and catalepsy.MethodStem bark of Lophira alata were obtained, identified, authenticated, dried and milled to fine powder. Extraction was done using ethanol; phytochemical screening and determination of the mean lethal dose were carried out.Analgesia was evaluated using the hot plate and acetic‐acid induced mouse writhing tests at graded doses of 200–800 mg/kg while haloperidol and reserpine induced catalepsy were carried out to determine anti‐cataleptic potential of Lophira alata. Muscle relaxant activity and sedative property were assayed via the rotarod and diazepam induced sleep tests respectively.ResultsReduction in number of writhes in the acetic acid induced mouse writhing and increase in latency time on the hot plate were observed at dose levels of 800 mg/kg. Lophira alata at 400 and 800 mg/kg significantly reduced mean cataleptic score while no significant difference between control groups and Lophira alata treated animals were observed in the rotarod and diazepam induced sleep tests.ConclusionLophira alata possesses anti‐cataleptic property and reduces algesia possibly via peripherally and centrally mediated mechanisms.Support or Funding InformationNo honorarium received

Chenopodium incisum Aerial Parts Extract Induces Anxiolytic-Like Effects in Mice

Chenopodium incisum Poir., Amaranthaceae, is employed as a remedy to alleviate susto, a culture-bound syndrome. This study evaluated the anxiolytic-like effect of a single oral dose of a hydroethanolic extract of C. incisum and two of its main constituents, pinostrobin and stigmasterol, in the elevated plus maze and hole-board test in mice. The nonspecific effects of the drugs on the ambulatory activity of mice were evaluated in the open field test. The acute toxicity of the extract was determined, and the extract composition was analyzed. The extract at 50, 100, and 200 mg/kg, as well as pinostrobin and stigmasterol (1 to 30 mg/kg), induced anxiolytic-like effects in both the elevated plus maze and in the hole-board tests, significantly increasing the exploratory behaviors. The anxiolytic actions of drugs were not associated with changes in the ambulatory activity of animals. No evidence of toxicity was observed in the animals treated with hydroethanolic extract of C. incisum. The mean lethal dose was higher than 2000 mg/kg. Chenopodium incisum elicited anxiolytic effects in mice. To the best of our knowledge, this is the first report regarding the anxiolytic effect of pinostrobin. Our results suggest that C. incisum is beneficial to patients with mood disorders.

Evaluation of anthelmintic drugs against egg development of rumen flukes recovered from cattle raised in the humid tropics of Mexico

Paramphistomosis is a parasitic disease endemic in ruminants nearly worldwide. In the present study, an in vitro screening of the main anthelmintics used in Mexico was carried out to determine the mean lethal dose for rumen fluke eggs from cattle in a humid, warm region. Rumen flukes were obtained from cattle slaughtered in the states of Tabasco and Chiapas in Mexico. Eggs were collected using a 37-μm sieve and quantified. Then, an in vitro incubation study was performed: 100 eggs were placed into the wells of polystyrene microtiter plates. Anthelmintic products were tested on the eggs at concentrations ranging from 0.0015 to 3.0 mg/ml for rafoxanide, 0.0025 to 10.20 mg/ml for nitroxinil and 0.0015 to 3 mg/ml for closantel to determine the median lethal dose (LD50) and maximum lethal dose (LD99). A control group (water) was included in each plate. Three different species of rumen flukes (Calicophoron brothriophoron, Calicophoron clavula and Paramphistomum cervi) belonging to five isolates were identified. Nitroxinil had the highest efficacy against rumen fluke eggs, with an LD50 of 0.11 to 65 μg/ml, whereas rafoxanide showed the lowest efficacy with an LD50 ranging from 500 to 1713 μg/ml. Closantel showed high variability in the LD50 among the different analysed isolates (17 to 122 μg/ml). The evaluated flukicidal drugs presented differential efficacy against the development of rumen fluke eggs. The efficacy of the drugs will vary depending on the geographical area of origin of the animals.

Toxicity of insecticides on Neotropical stingless bees Plebeia emerina (Friese) and Tetragonisca fiebrigi (Schwarz) (Hymenoptera: Apidae: Meliponini).

Use of pesticides in agroecosystems is considered a major cause of bees diversity losses in the Neotropics, where Plebeia emerina (Friese) and Tetragonisca fiebrigi (Schwarz) (Hymenoptera: Apidae: Meliponini) are wild pollinators of native and crop plants. The aim of this study was to know the acute lethal toxicity of acetamiprid, malathion, phosmet and spinosad insecticides on P. emerina and T. fiebrigi. We obtained the mean concentration and mean lethal dose (LC50 and LD50) and the mean survival of workers after oral and topical exposure to insecticides, respectively. The LC50 values (ng a.i./μl of diet) and the decreasing order of toxicity for P. emerina was spinosad (4.96) > malathion (18.75) > phosmet (97.33) > acetamiprid (4204.06), and for T. fiebrigi also was spinosad (5.65) > malathion (8.39) > phosmet (53.91) > acetamiprid (9841.32), when orally exposed. The LD50 values (ng a.i./bee) and the decreasing order of toxicity for P. emerina was spinosad (1.90) > malathion (10.90) > phosmet (19.54) > acetamiprid (6216.55) and for T. fiebrigi was malathion (29.29) ≥ spinosad (29.79) > phosmet (41.95) > acetamiprid (1421.23), when topically exposed. The mean survival (hours) of contaminated bees by malathion, phosmet, and spinosad, was 11.81, 7.20, and 12.32 for P. emerina and 8.55, 7.20, and 13.34 for T. fiebrigi when orally exposed; and was 4.87, 9.87 and 11.17 for P. emerina, and 4.87, 4.76, and 19.05 for T. fiebrigi when topically exposed. Malathion, phosmet, and spinosad were highly toxic, while acetamiprid was moderately toxic. Our results indicated that the insecticides tested, mainly malathion, phosmet, and spinosad may be harmful to P. emerina and T. fiebrigi, making it essential to propose measures to minimize their impact on wild pollinators.

TOXICOLOGICAL ASSESSMENT OF THE EXPOSURE TO SOME ARYLHETEROALKANECARBOXYLIC COMPOUNDS ON THE BODY

Introduction. One of the current medical and social problems is the intoxication of the body of workers that occurs during the production of medicines in chemical-pharmaceutical enterprises. In this regard, it is necessary to substantiate and develop a hygienic rationing of the content of harmful substances in the air of the working area. Materials and methods. Toxicity parameters (1-benzylindol-3-yl-thio) acetic acid (BTAA) and tris-(2-hydroxyethyl) ammonium-1-benzylindol-3-ylthioacetate (VM-7-02) were studied. Experimental studies were conducted on outbred rats and mice, rabbits and guinea pigs. Using standard physiological, biochemical, hematological and morphological parameters, the effect of the substance on the experimental animals was evaluated. The parameters of acute inhalation toxicity of substances were determined during the experiment in the chamber for inhalation primers using spectrophotometry to analyze the amount of the substance in the air of the chambers. Processing and interpretation of the information obtained was performed using the software package “Statistic 10.0”. Results. In terms of mean lethal doses (DL50), both xenobiotics can be classified as moderately hazardous substances of hazard class III, and there are no specific species and sex differences in the sensitivity of animals to the substances under study. Local skin reaction and signs of resorption of substances through intact skin are absent. The irritant effect on the mucous membranes of the eyes of tris-(2-hydroxyethyl) ammonium-1-benzylindol-3-ylthioacetate can be classified as weak. The ability to material accumulation in the body of the compound VM-7-02 is medium: the cumulation coefficient is 3.7. At BTAA cumulative abilities are even weaker - the coefficient is equal to 5.1. In the subacute experiment, they have a toxic effect mainly on the hepatorenal system. The threshold of acute inhalation action of BTAA is 100.7, VM-7-02-57.8 mg/m3. Conclusion. A tentative safe level of exposure to VM-7-02 in the air of the working area is recommended at 0.3 mg/m3, BTAA is recommended at 2.0 mg/m3. Compliance with this standard will minimize the risk to the health of workers.

Aeromonas hydrophila, an Emerging Causative Agent of Freshwater-Farmed Whiteleg shrimp Litopenaeus vannamei.

Aeromonas hydrophila is a well-known bacterial pathogen associated with mass mortalities in aquaculture. Yet, few reports are available on whiteleg shrimp-pathogenic A. hydrophila. In the present study, a virulent isolate WS05 was confirmed as a causative agent of diseased freshwater-cultured whiteleg shrimp and showed a mean lethal dose (LD50) value of 4.8 × 104 CFU mL−1. It was identified phenotypically and molecularly as an A. hydrophila strain, and exhibited susceptibility to several veterinary antibiotics extensively used in aquaculture, including cotrimoxazole, doxycycline, florfenicol, neomycin, and tetracycline. In view of the strongest inhibition zone of florfenicol against isolate WS05, the synergistic effect of the combinations of florfenicol and herb extracts was further evaluated, and the result indicated that Punica granatum extract was a potential synergist of florfenicol against isolate WS05 and the fractional inhibitory concentration index (FICI) for the florfenicol-P. granatum extract was calculated as 0.31. When combined with 7.81 mg mL−1 P. granatum extract, the minimum inhibitory concentration (MIC) of florfenicol against isolate WS05 was reduced from 0.50 to 0.03 mg L−1, and its activity against isolate WS05 was also enhanced with a significant reduction of ≥3.61 log in cell density after 24 h of treatment compared with that in the single drug treatment. In addition, the protective effect was potentiated by the combination of florfenicol and P. granatum extract, with a cumulative mortality of 36.66% (p < 0.05) and 33.33% (p < 0.05) lower than that in the single treatment with florfenicol and P. granatum extract after the challenge with isolate WS05 for seven days. As far as we know, this is the first study to describe whiteleg shrimp-pathogenic A. hydrophila and suggest P. granatum extract as a potential synergist of florfenicol against the A. hydrophila pathogen.

Toxicological evaluation of the ethanol extract of &lt;i&gt;Lophira alata&lt;/i&gt; (Ochnaceae) stem bark in rats

Though Lophira alata is used in ethnomedicine for the management of a host of central nervous and systemic diseases, the toxicity profile has not been investigated. This study evaluated the toxicological profile of the ethanol extract of Lophira alata stem bark in rats. The mean lethal dose was determined. Animals were treated with 50-800 mg/kg of the ethanol extract for four weeks after which body weight/organ ratio, haematological, biochemical (renal and hepatic) and lipid profile of test animals were evaluated. Changes in body weight and histopathological examination of brains, kidneys and livers were also carried out. Lower doses (50-400 mg/kg) did not affect body weight, organ/body weight ratio, hepatic, renal, haematological, lipid profile and morphology of organs of test animals. The highest dose affected creatinine levels, serum proteins and induced some histopathological changes. Lophira alata is relatively safe at low doses but high doses of Lophira alata should be used with caution.Keywords: Lophira alata; Toxicity; Lipd profile; Haematological indices

Transformación de Plomo Potencialmente Tóxico a Pb (NO3)2 Cristalino

La acumulación de plomo en el ambiente es una causa de problemas de salud en humanos. La dosis letal media reportada en mg/kg para Pb, Pb (NO3)2 y PbO es de 400, 2250 y 2000, respectivamente. Debido a la alta toxicidad del plomo metálico con respecto al nitrato de plomo se ha desarrollado una metodología para transformar el plomo residual a nitrato de plomo, cuya toxicidad es cinco veces menor que el plomo metálico. Por otra parte, el nitrato de plomo puede ser precursor para la síntesis de materiales con potencial aplicación industrial. La síntesis del Pb (NO3)2 se realiza mezclando el plomo metálico residual y ácido nítrico 15.7 molar en una proporción de reactivos [1:4]. Posteriormente, la mezcla se somete a agitación magnética hasta disolver el plomo y formar un precipitado blanco, se seca a 110 °C durante 1 h obteniendo un rendimiento experimental del 99 %. El material sintetizado se caracteriza por difracción de rayos–X, microscopía electrónica de barrido y espectroscopia por dispersión de energía. Así mismo, esta metodología tiene un impacto favorable en los ecosistemas, ya que la contaminación por plomo se verá disminuida.

DNA‑PKcs inhibitor increases the sensitivity of gastric cancer cells to radiotherapy.

Gastric cancer (GC) is a severe public health problem worldwide, particularly in China. Radiotherapy is the main locoregional treatment for various types of unresectable tumor, including GC. However, many patients fail to respond to radiotherapy due to the intrinsic radioresistance of cancer cells. This study was designed to investigate the effects and potential mechanism of radiosensitization associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor in human GC cell lines in vitro. Among the six GC cell lines (SGC7901, HGC-27, MKN45, MKN74, BGC823 and MGC803) that were exposed to increasing doses of IR (0, 2, 4, 6 and 8 Gy), the mean lethal dose and quasi-threshold dose measurements indicated that BGC823 and MGC803 were relatively insensitive to ionizing radiation (IR). IR induced significant elevation of γ H2A histone family member X (γH2AX) in MKN45 cells compared with BGC823 cells. DNA-PKcs and phospho-DNA-PKcs protein levels were increased in BGC823 and MGC803 cells compared with other GC cell lines (SGC7901, HGC-27, MKN45 and MKN74). DNA-PKcs inhibition led to increased sensitivity of BGC823 and MGC803 cells to IR. NU7441 increased γH2AX expression in the nuclei of BGC823 cells following IR. Combination of DNA-PKcs and CK2 inhibition further increased the sensitivity of GC cells to IR. The combination of NU7441 and CX4945 increased γH2AX expression in the nucleus of BGC823 cells following IR compared with treatment with NU7441 alone. Taken together, the findings suggest that DNA-PKcs inhibitor increased the sensitivity of radioresistant BGC823 and MGC803 cells to radiotherapy through the cleaved-caspase3/γH2AX signaling pathway, thus presenting a potential treatment method for GC.

Genetic Identification and Biological Characterization of Baculovirus Isolated from Helicoverpa armigera (Lepidoptera: Noctuidae) in Brazil

Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) larvae are polyphagous, aggressive, and have been found in many of Brazil's agricultural areas. Biological control with baculoviruses is part of an integrated pest management (IPM) strategy to manage this insect. Three isolates of nucleopolyhedrovirus (NPV) were collected from Brazilian populations of H. armigera, and compared genetically and biologically to Gemstar® (an imported nucleopolyhedrovirus), and to Nucleopolyedrovirus spodoptera (SPNPV) that was passed serially through H. armigera. Genetic sequencing of lef-8 and lef-9 genes revealed that the Brazilian isolates were closely related to nucleopolyhedrovirus species from Australia, South Africa, China, and India. The isolates caused high mortality rates in third instar H. armigera larvae. The mean lethal dose (LD50) and lethal time (LT50) differed between isolates, but was highest for HearNPV-BR2. This is the first report of HearNPV in Brazil, and the insecticidal properties of the BR2 isolate support its potential use in the production of biopesticides to manage H. armigera in Brazil.

Radiación gamma para inducción de mutagénesis en pasto rosado [Melinis repens (Willd.) Zizka

La radiación gamma puede ser utilizada para conocer el rango de radiosensibilidad (RRS) en pastos con fines de mejoramiento genético por mutagénesis. El pasto rosado es una especie invasora que puede ser mejorada en valor nutricional u otras características. El objetivo de este estudio fue determinar la dosis óptima de radiación gamma para inducir mutaciones efectivas en pasto rosado mediante dosis letal media (DL50) y reducción media de crecimiento (GR50). El estudio fue realizado en campo, laboratorio e invernadero. De acuerdo a la media ponderada de las variables incluidas en LD50 y GR50, la dosis óptima se estimó a los 304 Gy. Los resultados de este estudio permiten conocer el RRS para la aplicación de radiación gamma óptima con Co60, que pueda inducir características futuras de interés económico y ecológico en el pasto rosado.

Evaluation of the Toxicity Profile and Analgesic Property of Ethanol Extract of Lophira alata Stem Bark in Rodents

IntroductionLophira alata a woody tree found in West Africa is used in the management of pain, schizophrenia and convulsion. This study was carried out to evaluate the toxicity profile and analgesic activity of the of ethanol extract of Lophira alata in rats and mice respectively.MethodsStem bark of Lophira alata obtained were identified, authenticated, dried and reduced to fine powder. Phytochemical screening and determination of the mean lethal dose were carried out. Rats (n=30) in different groups were treated with 100–800 kg/mg of the extract daily for 28 days and monitored for weight loss and signs of toxicity. These animals where sacrificed at the end of the study and visceral organs isolated for histo‐pathological, biochemical and hematological assays.Analgesic property was evaluated in mice treated with graded doses (50–800 mg/kg) of the Lophira alata and subjected to either the mouse writhing assay or hot plate test. The tail flick test was used to determine analgesic activity in rats.ResultsThe mean lethal dose was determined to be 5000 mg/kg. No significant difference was observed between weights of animals treated with Lophira alata and the control groups. There was also no significant difference in organ weight ratios between treated and untreated animals. In the hematological assays, there was a decrease in erythrocytes with 800 mg/kg dose levels while a reduction in low density cholesterol was observed in the treated animals. In the mouse writhing test, treatment with Lophira alata decreased number of writhes but did not significantly affect the latency time in the tail flick test.ConclusionLophira alata is relatively safe for use and reduces algesia possibly via peripherally mediated mechanisms.Support or Funding InformationNo honorarium receivedThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

ANALYSIS OF RELATIONSHIPS BETWEEN THE CAPACITY OF CHEMICALS TO THE CUMULATION AND THE STRUCTURE OF THEIR MOLECULES

The relationships between the capacity of chemicals to cumulate a toxic effect (functional cumulation) and the structure of their molecules were investigated. In the process of substantiation of safe levels (MAC) of substances in water this capacity is characterized by the cumulation hazard class (later in the text - hazard class). This class is stated to be depend on the value of the relationship between the mean lethal dose of the acute experiment and the threshold dose of the chronic experiment. The experimental study of a huge amount of new chemicals in the chronic experiments is a very difficult task, thus the study of the possibility to predict the hazard class of a chemical is of great scientific and practical interest. By using a logical combinatorial method JSM, named in honor of an English logic J.S. Mill, the structural groups in molecules, determining the appurtenance of these chemicals to a hazard class were identified and the possibility of the prediction of the hazard class of a chemical belonging to a definite structural array, containing such structural group were investigated. The training dataset (583 compounds) was automatically derived from the database WATERTOX, containing the data on acute and chronic toxicity for about 2000 substances. The results suggest the JSM method to be limitedly applicable for the determination of a hazard class of an untested chemical using this heterogeneous training dataset because we were unable to unambiguously derive the list of chemicals belonging to the class of moderately hazard substances. The chemical in some cases was predicted to belong to one or other of the neighboring classes. However taking in mind this uncertainty, the accuracy of the method evaluated, when using the “leave-one-out” method was 78%. Nevertheless the JSM method enables us to find structural subgroups “responsible” for the functional cumulation. The relation of the hazard class of a chemical belonging to a definite structural class with its structure and the possibility of the prediction of an untested chemical hazard class are demonstrated. The prognosis of the hazard classes for chemicals belonging to several structural sets including the anthraquinone derivatives, phthalimides, perfluorated aliphatic compounds, chlorosubstituted phenols, phenylureas is performed.

Boosting the Radiosensitizing and Photothermal Performance of Cu2- xSe Nanocrystals for Synergetic Radiophotothermal Therapy of Orthotopic Breast Cancer.

The small difference between tumor and normal tissues in their responses to ionizing radiation has been a significant issue for radiotherapy of tumors. Herein, we report that dumbbell-shaped heterogeneous copper selenide-gold nanocrystals can serve as an efficient radiosensitizer for enhanced radiotherapy. The mean lethal dose of X-rays to 4T1 tumor cells can be drastically decreased about 40%, that is, decreasing from 1.81 to 1.10 Gy after culture with heterostructures. Due to the synergetic effect of heterostructures, the dose of X-rays is also much lower than those obtained from mixture of Cu2- xSe + Au nanoparticles (1.78 Gy), Cu2- xSe nanoparticles (1.72 Gy) and Au nanoparticles (1.50 Gy), respectively. We demonstrate that the sensitivity enhancement ratio of Cu2- xSe nanoparticles was significantly improved 45% ( i. e., from 1.1 to 1.6) after the formation of heterostructures with gold. We also show that the heteronanocrystals exhibit an enhanced photothermal conversion efficiency, due to the synergetic interactions of localized surface plasmon resonance. These properties highly feature them as a multimodal imaging contrast agent (particularly for photoacoustic imaging, computed tomography imaging, and single photon emission computed tomography after labeled with radioisotopes) and as a radiosensitizer for imaging guided synergetic radiophotothermal treatment of cancer. The research provides insights for engineering low- Z nanomaterials with high- Z elements to form heteronanostructures with enhanced synergetic performance for tumor theranostics.