LD50 Dose Research Articles

Dosimetrically Correlating the Acute Effect of Bone Radiation on Anemia in Men with Intact Prostate Cancer

<h3>Purpose/Objective(s)</h3> Published data evaluating the effect of radiation (RT) on pelvic bone marrow is mainly based on women with gynecological cancers receiving concurrent chemotherapy. The effect of RT on bone marrow in men with prostate cancer (PC) is less clear, where chemotherapy is not routinely delivered. This study aimed to determine if there is a dosimetric correlation between the volume of pelvic bone irradiated when treating PC and reduced hemoglobin (Hgb) values. Impaired marrow function affects patient quality of life and future systemic therapy. The a priori hypothesis was that volume of pelvic bone receiving at least 4 Gy (V4Gycc) would correlate significantly with marrow toxicity, given that 4Gy is the LD50 dose for a total body exposure. <h3>Materials/Methods</h3> A prospective database of PC patients treated at one institution was utilized. Non-metastatic patients treated between 2008 and 2021 with definitive RT were selected. Patients were included if they had at least one Hgb value within two years prior to their RT start date and at least one Hgb value within three years of RT completion. Patients with confounding diagnoses were excluded and were censored at the time of a second oncologic treatment course or confounding event known to lower Hgb levels. All patient charts were individually audited for accuracy. Pelvic bone (L3/L4 interface through ischial tuberosities) was contoured, and the dose to this structure was calculated. Doses were converted to 2 Gy equivalent doses (EQD2) using an α/β of 10. Exploratory analysis suggested dichotomizing into low volume exposures (LVE; V4Gycc <=1000cc) and high-volume exposures (HVE, V4Gycc >1000cc). Non-parametric kernel regressions evaluating the effects of time, V4Gycc, and androgen deprivation therapy (ADT) use on Hgb values was performed. Percent reduction in Hgb from baseline was evaluated. <h3>Results</h3> 222 patients were included in final analysis. Median starting Hgb was 15.0 g/dL (IQR 14.2-15.9). The mean V4Gycc was 1283cc (IQR 1740-2044). Hgb nadir occurred around day 90 post-RT start. Both HVE and LVE groups had significantly lower Hgb as a percentage of baseline at day 90 (HVE= 85.4%, p < 0.001; LVE=94.8%, p < 0.001). HVE resulted in significantly lower Hgb levels compared to LVE at day 90 (95% confidence intervals; 80.3% - 88.9% vs 90.9% - 98.3%, p < 0.001). ADT use had no effect on Hgb levels (p = 0.45). Kernel-weighted local polynomial smoothing implies HVE also have impaired marrow recovery compared to V4Gycc < 1000. <h3>Conclusion</h3> In prostate cancer treatment, a V4Gycc of bone marrow >1000 results in significantly lower Hgb nadir as a percentage of baseline than patients who received V4Gycc < 1000. Our model predicts that if a patient receives V4Gycc to pelvic bone marrow >1000, they will become mildly anemic with a baseline Hgb of 15.2, moderately anemic with a baseline Hgb of 12.8, and severely anemic with a baseline Hgb of 9.3. Limiting pelvic bone marrow to <1000cc receiving ≥4Gy EQD2 is a proposed dose constraint to limit acute marrow toxicity.

Immunogenicity and protective efficacy of the recombinant Pasteurella multocida lipoproteins VacJ and PlpE, and outer membrane protein H from P. multocida A:1 in ducks.

Duck cholera (duck hemorrhagic septicemia) is a highly contagious disease caused by Pasteurella multocida, and is one of the major bacterial diseases currently affecting the duck industry. Type A is the predominant pathogenic serotype. In this study, the genes encoding the lipoproteins VacJ, PlpE, and the outer membrane protein OmpH of P. multocida strain PMWSG-4 were cloned and expressed as proteins in E. coli. The recombinant VacJ (84.4 kDa), PlpE (94.8 kDa), and OmpH (96.7 kDa) proteins were purified, and subunit vaccines were formulated with a single water-in-oil adjuvant, while killed vaccines were prepared using a single oil-coated adjuvant. Antibody responses in ducks vaccinated with recombinant VacJ, PlpE, and OmpH proteins formulated with adjuvants were significantly antigenic (p<0.005). Protectivity of the vaccines was evaluated via the intraperitoneal challenge of ducks with 20 LD50 doses of P. multocida A: 1. The vaccine formulation consisting of rVacJ, rPlpE, rOmpH, and adjuvant provided 33.3%, 83.33%, and 83.33% protection, respectively, the vaccine formulation consisting of three recombinant proteins, rVacJ, rPlpE, rOmpH and adjuvant, was 100% protective, and the killed vaccine was 50% protective. In addition, it was shown through histopathological examination and tissue bacterial load detection that all vaccines could reduce tissue damage and bacterial colonization to varying (p<0.001). These findings indicated that recombinant PlpE or OmpH fusion proteins formulated with oil adjuvants have the potential to be used as vaccine candidates against duck cholera subunits.

Freezing stress affects the efficacy of clodinafop-propargyl and 2,4-D plus MCPA on wild oat (Avena ludoviciana Durieu) and turnipweed [Rapistrum rugosum (L.) All.] in wheat (Triticum aestivum L.).

The occurrence of freezing stress around herbicides application is one of the most important factors influencing their performance. This experiment was performed to evaluate the efficacy of clodinafop-propargyl and 2,4-D plus MCPA (2,4-Dichlorophenoxyacetic acid plus 2-methyl-4-chlorophenoxyacetic acid), the most important herbicides used in wheat fields in Iran, under the influence of a freezing treatment (-4°C). Wheat and its two common weeds, winter wild oat (Avena ludoviciana Durieu) and turnipweed [Rapistrum rugosum (L.) All.], were exposed to the freezing treatment for three nights from 7:00 P.M. to 5:00 A.M. before and after herbicide application, and their response was compared with plants that did not grow under freezing stress. Under no freezing (NF) and freezing after spray (FAS) conditions, winter wild oat was completely controlled with the recommended dose of clodinafop-propargyl (64 g ai ha-1; hereafter g ha-1). However, the survival percentage of winter wild oat in the freezing before spray (FBS) of clodinafop-propargyl 64 g ha-1 was 7%, and it was completely controlled with twice the recommended dose (128 g ha-1). Under NF conditions and FAS treatment, turnipweed was completely controlled with twice the recommended dose of 2,4-D plus MCPA (2025 g ae ha-1; hereafter g ha-1), while there was no complete control under recommended rate. However, in the FBS treatment, the survival of turnipweed was 7% under double dose. The LD50 (dose required to control 50% of individuals in the population) and GR50 (dose causing 50% growth reduction of plants) rankings were NF<FBS<FAS for clodinafop-propargyl and NF<FAS<FBS for 2,4-D plus MCPA. Selectivity index for clodinafop-propargyl in NF conditions, FBS, and FAS treatments was 2.4, 0.91, and 0.78, respectively, and, for 2,4-D plus MCPA, it was 2.6, 0.12, and 0.88, respectively. According to the results of LD50, it can be stated that the freezing stress after the spraying of clodinafop-propargyl and before the spraying of 2,4-D plus MCPA would further reduce the efficacy of these herbicides.

LD50 and affective dose of Eruca sativa mill (gergeer) ethanolic extract

Cardiotoxicity is defined as drug-induced damage to the heart muscle, which can result in cardiac failure or cardiac arrest. Cardiotoxicity is a common side effect of traditional anticancer drugs such as doxorubicin, taxanes, 5-fluorouracil, and cyclophosphamide, as well as newer agents such as biological antibodies such as Nivo. Cardiotoxicity is also caused by the long-term use of neurologic/psychiatric medications. This study was designed to determine the effect of eruca sativa mill (Gergeer) leaves extract on cardiotoxicity induced by doxorubicin in rabbits. The fifty-four rabbits used in this study were obtained from a local rabbit breeder. Animals ranged between 1-1.3 years old, and their weight was approximately 1-2kg without specifying gender experiment Acute toxicity study, The pilot study to determine the LD50 dose of Eruca sativa mill (gergeer) by "up and down" method after acute exposure in rabbits, The effective dose of Eruca sativa mill (gergeer) was determined by using a simple line equation. The effective dose of Eruca sativa. troponin I determine the level of proteins in the blood increase in heart attack,.The Troponin-I level of the control positive group revealed a significant increase as compared with G3, G4, G5, and the control negative group.The cTn-I level of the G3 significant increase is compared with treated G4,G5 group and control negative group with a significant decrease is compared with G1, G2 group and control positive group ; while treated G4 ,G5 group significant decrease is compared with treated G1,G2,G3 group and control positive, Log number dose-response curve and maximum effective dose the simple line equation revealed that the effective Eruca sativa dose of Troponin I level was (3.01 , 2.99 ,1.97 ,1.015, 1.030) (ng/ml) respectively, whereas the effective Eruca sativa dose of Troponin I was 316 mg/kg. conclusion , The effective dose-response results asymptotic to 10 % of LD50, induced cardiac toxicity with DOX appear biochemically, cardiographycally and histopathologically, The Eruca sativa mill (gergeer) extract was effective protective for induced cardiac toxicity.

Determination of Radio Sensitivity (LD50) of Embryo Cultured of Banana (Musa balbisiana) cv. Bhimkol

Banana is parthenocarpic and vegetatively propagated crop due to which in vitro mutagenesis approaches have substantial scope to create variations for crop improvement. Bhimkol cultivar is a wild seeded type and it set seeds naturally. The immature seeds can be used for the in vitro mutation to create variability. Prerequisite in an in vitro mutation study, is to determine the appropriate dosages to produce larger recovery of mutants with diminutive population loss. It is necessary to fix the lethal dose (LD50) for optimizing the radiation doses for immature seeds of banana. In the present investigation, in order to fix the LD50 value immature seeds of banana were subjected to five different doses of gamma irradiation ranged from 5-25 Gy with control (untreated). The present finding was observed that as gamma radiation dose increased, delayed germination and reduction in the germination percentage of immature embryos. And also, seedling height and root length reduced significantly. Based on the probit analysis curve, the germination percentage showed that, LD50 dose of gamma radiation was 15 - 20 Gy for higher germination percentage of immature embryos in banana cv. Bhimkol.

Histological and ultrastructural changes in rat kidneys in the early period after paraoxone poisoning

Introduction. Toxic nephropathies are not limited to a single morphological type of kidney tissue damage. The widespread distribution of organophosphorus compounds (OPs) in the modern world makes it necessary to study the morphological manifestations and delayed effects of OPs on various organs and tissues of the human and animal body. Material and methods. The article presents the results of a study of changes in the kidneys of rats at the ultrastructural level in the early stages after a single injection of paraoxon at doses of LD50 and LD84. Results. It has been shown that after the introduction of paraoxon, the epithelial cells of the convoluted tubules are initially damaged, and a week after the poisoning, changes are recorded in the renal corpuscle, manifested in an increase in the thickness of the glomerular basement membrane. Limitations. Morphological changes in the renal tissues were analyzed in a single poisoning at doses of LD50 and LD84. Conclusion. The changes detected in the renal corpuscles indicate the feasibility of further studies on the effect of FOS on the nature, sequence and mechanism of nephrotoxic effects of FOS in models of acute and chronic intoxication.

Effectiveness of various regimens of systemic anti-inflammatory therapy with glucocorticoids in the development of acute LPS-induced lung damage in the experiment

BACKGROUND: When studying new and effective methods of treating acute respiratory distress syndrome, an immunogenic model of lung injury occupies a special place. To date, the search for the optimal strategy and regimen for the use of glucocorticoids in the development of acute respiratory distress syndromе is relevant.&#x0D; AIM: The article evaluates the effectiveness of various schemes of systemic anti-inflammatory therapy with glucocorticoids in an experimental model of acute LPS-induced lung injury.&#x0D; MATERIALS AND METHODS: The study was conducted on 100 outbred male rats. Acute lung injury was modeled using an experimental model of direct acute lung injury by a single intratracheal injection of lipopolysaccharide (LPS) from the cell wall of the bacterium Salmonella enterica (Sigma-Aldrich) at a dose of LD50 (20 mg/kg). All animals were divided into groups (20 each): 1 intact rats; 2 control group (LPS + saline); 3 LPS + dexamethasone 0.52 mg/kg (small doses); 4 LPS + dexamethasone 1.71 mg/kg (average doses); 5 LPS + dexamethasone 8 mg/kg (high doses). The drugs were administered intraperitoneally once a day for 3 days. Dexamethasone doses were calculated using the interspecies dose transfer method using a factor that takes into account differences in body surface area.&#x0D; RESULTS: It has been established that an experimental model based on the endotracheal administration of S. enterica leads to the development of mortality from pulmonary causes. According to a preclinical study, the systemic use of low doses of dexamethasone (0.52 mg/kg) was found to be better than higher doses (1.71 mg/kg, 8 mg/kg) in the treatment of acute LPS-induced lung injury.

Resolving the acute gamma irradiation and ethyl methanesulphonate induced lethality for Jasminum sambac L. (Aiton) cv. Ramanathapuram Gundumalli

Crop improvement in Jasminum sambac through induced mutagenesis entails the insight on the sensitiveness of the individual plant materials of a species to different classes and nature of the mutagens. The current assessment was undertaken to analyse the mutagenic effect of acute gamma irradiation and EMS in Jasminum sambac cv. Ramanathapuram Gundumalli. Semi-hardwood cuttings of the plants were exposed to different dosage levels of gamma rays varying from 0 Gy (control) to 40 Gy and decapitated rooted cuttings were treated with EMS from 0 mM (control) to 90 mM. The M1V1 generation was evaluated by treating the cuttings with four different doses of gamma rays (15 Gy, 20 Gy, 25 Gy and 30 Gy) and three concentrations of EMS (45 mM, 60 mM, 75 mM) formulated using respective LD50 doses.&nbsp; The lethality dosage (LD50) value for the cultivar Ramanathapuram Gundumalli was determined to be 21.37 Gy and 64.57 mM for gamma irradiation and EMS, respectively applying the probit curve analysis. The maximal reduction in the survival of cuttings of 75% and 71% correspondingly in gamma and EMS treatments was discerned at higher doses in comparison to the lower doses. The plants studied in M1V1 generation for growth and flowering characters exhibited variable responses pertaining to differing doses or concentrations of the specific mutagenic means. Keywords: Jasminum sambac, gamma irradiation, EMS, LD50 and semi-hardwood cuttings

Effect of the Bitis arietans snake venom obtained from Kaltungo, Nigeria on Liver Oxidative Stress Status and Histological changes in Wistar Albino Rats

The venom of the Nigerian Bitis arietans (puff adder) was assessed for its ability to trigger venom-induced necrosis as well as oxidative stress in the liver of Wistar albino rats. The snake was captured in Kaltungo Gombe state and the venom was milked and lyophilized accordingly. A single LD50 dose (1.5mg/kg) was administered and the rats were monitored for two weeks and the liver homogenate samples were analyzed for the changes in oxidative stress markers. Histopathology of the liver tissue was conducted to assess the necrotic effect of the venom. The Malondialdehyde (MDA) values were not significantly changed while the superoxide dismutase (SOD) and reduced glutathione (GSH) levels were affected significantly. One week after venom administration, the branching and anastomoses of the hepatocytes in the liver tissue were observed to be not clearly demarcated due to the severity of the necrosis with disintegrated nuclei especially in the wall of the central vein. There was almost total disintegration of the wall of the central vein two weeks after venom administration. The results of this study indicate that the Nigerian puff adder venom can also trigger oxidative stress and promote necrosis in the liver tissue of Wistar albino rats.

Estimation the Safety of Parenteral Resveratrol in Mice

Resveratrol is polyphenolic compound has many biochemical and biological effects on several organs. Therefore, resveratrol can be used to treat many diseases. The aim was to evaluate resveratrol safety when used in a parenteral single bolus dose. This study was conducted on 60 mice (30 males and 30 females). Each male and female mice divided into 6 groups (five mice per group). All mice groups given 1% DMSO and five different doses of resveratrol (5, 2.5, 1.25, 0.625, 0.312) gm/kg intraperitonially given to five groups respectively. The mice were continuously monitored during 14 days. The number of deaths, changes in general behavior, changes in physiological activity, and signs of toxicity were reported. On day 15 blood was collected using a jugular vein puncture to obtain blood samples for hematological and biochemical analysis. All mice were euthanized under anesthesia. The heart, lung, liver, kidney, and gonads were dissected and sent for histopathological study. The result showed that at dose 0.312gm/kg neither signs of toxicity nor death were detected. The LD50 dose was 1.18 g/kg for female and 1.07 g/kg for male mice. The body weight change, biochemical and hematological assay, revealed that at doses 1.25 g/kg,0.625,0.312 g/kg for both sexes no significant changes had reported in comparison with a control group (p?0.05). Histopathological examination revealed that at doses 1.25 g/kg for both sexes no significant tissue changes had reported in comparison with a control group (p?0.05). In conclusion resveratrol has dose-dependent toxicity when used intraperitoneally in Swiss Albino mice and the non-observed adverse effect level at dose 0.312 g/kg.

Determination of the embryotoxic effect of maropitant using an in ovo model.

The aim of this research was to determine the embryotoxic and teratogenic effects and lethal dose (LD50) of maropitant in ovo, using fertile chicken eggs. The study was designed in two stages, CHEST-I and CHEST-II. For CHEST-I, 210 fertile eggs were divided into seven equal groups; control, saline solution and 5 different doses of maropitant (10, 5, 2.5, 1.25, 0.625 mg/kg) injected groups. For CHEST-II, 150 fertile eggs were divided into five equal groups; control, saline solution and 3 different doses of maropitant (8, 6, 4 mg/kg)-injected groups. Eggs were opened on day 21 of incubation. Maropitant did not cause teratogenicity at any dose, while higher embryonic death rates were observed at doses above 4 mg/kg. The LD50 dose of maropitant was determined as 7.24 mg/kg. In conclusion, maropitant should only be used after full consideration of risks and benefits in pregnancy.

Alcohol binge drinking decreases brain glucose metabolism and functional connectivity in adolescent rats.

Alcohol misuse represents a serious health concern, especially during adolescence, with approximately 18% of high school students engaging in binge drinking. Despite widespread misuse of alcohol, its effects on how the brain functions is not fully understood. This study utilized a binge drinking model in adolescent rats to examine effects on brain function as measured by brain glucose metabolism (BGluM). Following an injection of [18 FDG] fluro-2-deoxy-D-glucose, rats had voluntary access to either water or various concentrations of ethanol to obtain the following targeted doses: water (no ethanol), low dose ethanol (0.29 ± 0.03g/kg), moderate dose ethanol (0.98 ± 0.05), and high dose ethanol (2.19 ± 0.23g/kg). Rats were subsequently scanned using positron emission tomography. All three doses of ethanol were found to decrease BGluM in the restrosplenial cortex, visual cortex, jaw region of the somatosensory cortex, and cerebellum. For both the LD and MD ethanol dose, decreased BGluM was seen in the superior colliculi. The MD ethanol dose also decreased BGluM in the subiculum, frontal association area, as well as the primary motor cortex. Lastly, the HD ethanol dose decreased BGluM in the hippocampus, thalamus, raphe nucleus, inferior colliculus, and the primary motor cortex. Similar decreases in the hippocampus were also seen in the LD group. Taken together, these results highlight the negative consequences of acute binge drinking on BGluM in many regions of the brain involved in sensory, motor, and cognitive processes. Future studies are needed to assess the long-term effects of alcohol binge drinking on brain function as well as its cessation.

Topiramate and Acetazolamide Combination a Comparative Study between High and Low Dose Profile of Side Effects on Metabolism

Background: Topiramate, with multiple putative anticonvulsant pathways, is a relatively recent antiepileptic drug. The ability to inhibit carbonic anhydrase, a property common with the acetazolamide anticonvulsant, is among them. Aim: The study refers to compare between the use of combinations of topiramate and acetazolamide high and low doses of drugs and which one is safer for the patients. Methods: Twenty stable adult males wistar rats three weeks after acclimatization and uniformly split into two groups (10 rats in each group) and 60 days of treatment: 9 mg/kg/B.W of Topiramate and 30 mg/kg/B.W of Acetazolamide in the high dose (Hd) group and 5 mg/kg B.W of Topiramate and 30 mg/kg B.W of Acetazolamide in the low dose (Ld) group, orally/day in the high dose (Hd) group. Results: No major differences in mean Glutamate pyruvate transaminase, Glutamic oxaloacetic transaminase, Alkaline phosphatase concentration were found in the statistical analysis of the results in all experimental groups compared with each other at the pretreated period, also revealed that intubation of rats in the 60-days Hd induced a substantial (P&gt;0.05) rise in the mean Glutamate Pyruvate Transaminase and Glutamic Oxaloacetic Transaminase serum concentrations relative to the control and Ld classes. Treatment of low-dose rats showed a substantial (P&lt;0.05) decrease in serum alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine enzyme concentrations at 30 and 60 days of the trial compared with the T1 group. Conclusion: The study showed that high-dose combinations of topiramate and acetazolamide had the same adverse effect somewhat in low-dose combinations.

Octanoic Acid-An Insecticidal Metabolite of Conidiobolus coronatus (Entomopthorales) That Affects Two Majors Antifungal Protection Systems in Galleria mellonella (Lepidoptera): Cuticular Lipids and Hemocytes.

The food flavour additive octanoic acid (C8:0) is also a metabolite of the entomopathogenic fungus Conidiobolus coronatus, which efficiently infects and rapidly kills Galleria mellonella. GC-MS analysis confirmed the presence of C8:0 in insecticidal fraction FR3 extracted from C. coronatus filtrate. Topical administration of C8:0 had a dose-dependent effect on survival rates of larvae but not on pupation or adult eclosion times of the survivors. Topically applied C8:0 was more toxic to adults than larvae (LD100 for adults 18.33 ± 2.49 vs. 33.56 ± 2.57 µg/mg of body mass for larvae). The administration of C8:0 on the cuticle of larvae and adults, in amounts corresponding to their LD50 and LD100 doses, had a considerable impact on the two main defense systems engaged in protecting against pathogens, causing serious changes in the developmental-stage-specific profiles of free fatty acids (FFAs) covering the cuticle of larvae and adults and damaging larval hemocytes. In vitro cultures of G. mellonella hemocytes, either directly treated with C8:0 or taken from C8:0 treated larvae, revealed deformation of hemocytes, disordered networking, late apoptosis, and necrosis, as well as caspase 1–9 activation and elevation of 8-OHdG level. C8:0 was also confirmed to have a cytotoxic effect on the SF-9 insect cell line, as determined by WST-1 and LDH tests.

Criteria of reversibility of suppression of bioelectric activity of the brain in alcoholic coma: experimental study

The aim. The aim of the study is to determine prognostically significant criteria for the reversibility of the suppression of the generation of bioelectrical activity using an experimental model of alcoholic coma. Materials and methods. The work was performed on 27 nonlinear sexually mature rats weighing 340±40 g, which received a 40% solution of ethyl alcohol by the oral route in fractional doses of 12.6 g/kg, which corresponded to LD50. EEG monitoring was performed until there was a definite effect (from 1 to 54 hours). Results. In a favorable outcome of alcoholic coma (11 rats), the EEG results contained the following phase states: 1) a pattern of continuous activity with registration of flashes with intense modulation amplitudes (modulation coefficient 10-12, index 25-35%); 2) a pattern of discrete activity (signal suppression index does not exceed 10%), which was recorded only in the toxicogenic phase; 3) a pattern of awakening. In the lethal outcome of cerebral insufficiency (16 rats), there were the following states of bioelectric activity: 1) weakly modulated continuous activity (modulation coefficient is less than 5); 2) fragmented activity (suppression index is 20-50%); 3) “flash-suppression” pattern; 4) a pattern of periodic discharges; 5) isoelectric silence. The terminal phase of cerebral insufficiency was characterized by the presence of high-amplitude waves with a frequency of 1-1.5 Hz, alternating with 3-4 oscillations decreasing in amplitude. Conclusion. In a case of acute poisoning with ethanol at a dose of LD50, the prognostically favorable EEG sign is the amplitude modulation of continuous activity, which reflects the preservation of synchronizing thalamocortical interactions. In the toxicogenic phase of the poisoning, a pattern of discrete activity can be recorded (modulation index is up to 10%), which reflects the suppressive effect of ethanol rather than the decay of the bioelectrogenesis mechanisms.

Evaluation of orellanine-induced toxicity from the mushroom Cortinarius orellanus and the antagonistic effect of Petroselinum crispum

Mushroom poisoning is a worldwide public health problem that may cause serious toxic consequences on renal functions. The study aimed to evaluate the acute toxicity (24 h) of orellanine (OR) from Cortinarius orellanus in rat kidney and the ameliorative effect of parsley ethanolic extract. Twelve adult male Wistar rats were used to determine intraperitoneal (ip) median lethal dose (LD50) of OR, and 32 rats were divided into 4 groups (n = 8): OR group had 500 mg OR per kg bwt; OR + parsley group had the same dose of OR and after 1 h had 500 mg/kg parsley orally; parsley group had parsley only; and control had the vehicle 0.1% DMSO. Blood and kidney samples were collected at Hour 48. The LD50 dose was 1430 mg/kg for an observation period of 24 h. There were significant reductions (p < 0.01) in the body weight, and relative kidney weight of intoxicated rats compared to parsley treated rats and to controls. Similarly, this group had significantly higher levels of creatinine (p < 0.001), uric acid and urea (p < 0.05). The antioxidant glutathione peroxidase activity was significantly reduced (p < 0.01), while Cystatin C serum levels were significantly higher (p < 0.001) in the intoxicated untreated rats compared to all groups. Histopathological examination indicated necrotic damage in glomeruli and proximal tubules of rats given OR, which was relieved by parsley extract. Overall, the study showed that parsley extract ameliorated OR-induced kidney toxicity. This could be utilized in future research on adjunct therapy for toxicity-induced renal injury.

Acute oral toxicity of Essential oil extracted from the leaves of Ocimum sanctum L. (Thulasi) in female Wistar albino rats.

Due to the widespread use of antimicrobial agents, many Microorganisms have developed drug resistance to many available antimicrobials today. Essential oils from different plants are being explored for their ability to treat various human diseases, including infectious diseases. Earlier, we have found that the essential oil from the leaves of Ocimum sanctum L. had anti bacterial effect on 18 human pathogenic bacteria. In the present study, the essential oil of Ocimum sanctum L. was evaluated for its toxic effects at 300 mg / Kg body weight and 2000 mg / Kg body weight of female Wistar albino rats as per the OECD Guidelines 423 for testing of chemicals. The 14 day acute oral toxicity test has shown Ocimum sanctum L. essential oil is not toxic at 300 mg / Kg body weight of animals but has some toxic effects at 2000 mg /Kg body weight of animals. However, no animals died during the 14 day acute oral toxicity test with 2000 mg / Kg body weight of animals and therefore the LD50 dose of Ocimum sanctum L. should be more than 2000 mg / Kg of body weight of female Wister albino rats.

Neutralizing Monoclonal Antibody, mAb 10D8, Is an Effective Detoxicant against Abrin-a Both In Vitro and In Vivo.

Abrin is a types II ribosome-inactivating protein (RIP) isolated from Abrus precatorious seeds, which comprises a catalytically active A chain and a lectin-like B chain linked by a disulfide bond. Four isotoxins of abrin have been reported with similar amino-acid composition but different cytotoxicity, of which abrin-a is the most potent toxin. High lethality and easy availability make abrin a potential bioterrorism agent. However, there are no antidotes available for managing abrin poisoning, and treatment is only symptomatic. Currently, neutralizing antibodies remain the most effective therapy against biotoxin poisoning. In this study, we prepared, identified, and acquired a high-affinity neutralizing monoclonal antibody (mAb) 10D8 with a potent pre- and post-exposure protective effect against cytotoxicity and animal toxicity induced by abrin-a or abrin crude extract. The mAb 10D8 could rescue the mouse injected intraperitoneally with a 25 × LD50 dose of abrin-a from lethality and prevent tissue damages. Results indicated that 10D8 does not prevent the binding and internalization of abrin-a to cells but inhibits the enzymatic activity of abrin-a and reduces protein synthesis inhibition of cells. The high affinity, good specificity, and potent antitoxic efficiency of 10D8 make it a promising candidate for therapeutic antibodies against abrin.

Glutathione S-Transferase Genes are Involved in Lambda-Cyhalothrin Resistance in Cydia pomonella via Sequestration.

Pest management is mostly accomplished by the use of insecticides. However, the overuse of insecticides has led to the development of resistance. Glutathione S-transferases (GSTs) are vital detoxification enzymes involved in insecticide resistance in insects. In this study, we report the involvement of GSTs in insecticide resistance to lambda-cyhalothrin in Cydia pomonella, a globally quarantined fruit pest. A total of 25 GST, including 22 cytosolic genes and 3 microsomal genes, are identified from the genome database of C. pomonella. These cytosolic genes are further classified into six classes, including four in delta, eight in epsilon, three in omega, three in sigma, one in theta, and one in zeta class, as well as two unclassified genes. The real-time quantitative polymerase chain reaction (RT-qPCR) shows that the majority of these genes are mainly expressed throughout the larval stage and in the midgut of the fourth-instar larvae. Exposure to an LD10 dose of lambda-cyhalothrin resulted in the upregulation of 17 GST genes. Moreover, mRNA levels of most GST genes, with the exception of CpGSTe6, CpGSTd2, CpGSTd4, and CpGSTz1, are considerably higher in a lambda-cyhalothrin-resistant population (ZW_R) than those of susceptible strains. Recombinant CpGSTd1, CpGSTd3, CpGSTe3, and CpGSTs2 can bind and metabolize lambda-cyhalothrin, with the highest metabolic rate observed for CpGSTd3 but no metabolite(s) was detected, supporting the role of GSTs in sequestration of lambda-cyhalothrin. Molecular dynamics simulation analysis indicates that key residues of hydrophobic pocket-derived lipophilic energy S(lipo) interactions with a hydrophobic pharmacophore of lambda-cyhalothrin are crucial for metabolism by CpGSTd3 and further lead to resistance. Our study is the first to experimentally confirm the involvement of GSTs in lambda-cyhalothrin resistance via sequestration and provides new insights into resistance management in C. pomonella.

Enhancement of the Yersinia pestis EV NIIEG Vaccine Srain Immunogenic and Protective Activity under Cultivation with Azoxymer Bromide (Polyoxidonium)

Background. The live-attenuated vaccine based on the Yersinia pestis strain EV line NIIEG is still used in Russia, providing protective efficacy against plague. Nevertheless, there is an urgent need for developing new ways to increase the immunogenicity of the Y. pestis EV NIIEG vaccine strain. In this study, the ability of direct action of immunoadjuvant azoximer bromide (polyoxidonium, PO) on the immunobiological properties of vaccine strain Y. pestis EV NIIEG during cultivation on a dense nutrient medium was evaluated.Materials &amp; Methods. Y.pestis EV NIIEG, cultivated at 28 °С for 48 h on LB agar, Miller pH 7.2 ± 0.1 (Sigma-Aldrich, USA) with the addition of PO and without. MALDI-TOF mass-spectrometry was deployed for the obtainment of mass-spectra of ribosomal proteins from Y. pestis EV NIIEG cells on the MicroflexTM LT mass spectrometer (Bruker Daltonics, Germany). Protective efficacy was evaluated under subcutaneously challenge guinea pigs and mice BALB's with 400 LD50 doses of the Y. pestis 231, Y. pestis P-13268 Vietnam (MLD=5 CFU). Antibody titers to F1 in serum were determined using an ELISA.Results. The addition of the therapeutic concentration of PO in the cultivation medium induced a significant increase in the immunogenicity of Y. pestis EV NIIEG that resulted in enhancement of serum antibody levels against Y. pestis F1 antigen and several times the growth of protective efficacy in the bubonic plague model on two types of experimental animals. ImD50 of the vaccine strain Y. pestis EV NIIEG, cultivated with PO, was significantly (p &lt; 0,05) lower in comparison to ImD50 for Y. pestis EV NIIEG in standard cultivation conditions. One year of storage at a temperature of 4 °С did not alter the protective properties of the vaccine strain Y. pestis EV NIIEG, cultivated with PO.Conclusions. Morphological studies confirmed the absence of influence PO introduction into the cultivation environment on the safety of the vaccine strain. MALDI-TOF MS profile of the Y. pestis EV NIIEG, cultivated with PO, had peaks characteristic features. The mass peak at m/z 3,061 was significantly down-regulated and new mass peaks at m/z 2,759, m/z 3,533 were determined. These changes are accompanied by the increase of Y. pestis EV NIIEG immunogenicity.