scholarly journals Atrazine induced In vivo immunotoxic studies in Bivalves

2021 ◽  
Author(s):  
Muhammed Zafar Iqbal Abdul Rahim Navalgund ◽  
Muhammed Azghar Iqbal Navalgund
Keyword(s):  
Innate Immunity ◽  
Acute Toxicity ◽  
Broad Spectrum ◽  
T Test ◽  
Perna Viridis ◽  
Phagocytic Function ◽  
One Way Anova ◽  
Lethal Doses

Atrazine is ubiquitously used broad-spectrum herbicide to control the weeds in agriculture. The present study aimed to evaluate the acute toxicity and immunotoxicity of Atrazine in two ecologically and economically important bivalves. Acute toxicity of atrazine evaluated in triplicates by taking control and six experimental groups each comprising of 30 animals and treated with a range of atrazine from 2 PPM to 12 PPM for 96 hours. Mortalities were recorded for every 24 hours until 96 hours and data analyzed by one-way ANOVA and Dunnett T-test. The results indicated a significant increase in mortalities with increase in dose and time of exposure in both species. The values of LC50 were determined as 6.10 PPM and 4.90 PPM respectively for Perna viridis and Paphia malabarica. Furthermore, the immunotoxic potential of atrazine assessed by treating mussels and clams with the five sub-lethal doses of atrazine for 14 days and quantifying the viability of hemocytes by using simple yet reliable Tryphan blue exclusion assay. The results of the present study suggest atrazine-induced immunotoxicity by decreasing the number of viable hemocytes in bivalves. Hemocytes with phagocytic function are indispensable to confer innate immunity in bivalves, decreased viability of these cells leads to compromised immunity. This study is first of its kind to implicate atrazine with the immunotoxicity in bivalves.

scholarly journals Antitrypanosomal Effect of Hydromethanolic Extract of Solanum anguivi Lam on Field Isolates of Trypanosoma congolense Infected Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Debela Abdeta ◽  
Solomon Mequanente Abay ◽  
Mirutse Giday ◽  
Nigatu Kebede ◽  
Getechew Terefe
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Phytochemical Analysis ◽  
Mosquito Vector ◽  
Test Results ◽  
Control Groups ◽  
Prolonged Incubation ◽  
Field Isolates ◽  
One Way Anova

Introduction. Trypanosomiasis is one of the world’s most serious infectious diseases caused by Trypanosoma parasites. Concern about resistance to conventional antitrypanosomal drugs, mosquito vector resistance to existing insecticide side effects of existing antitrypanosomal drugs justifies the urgent need for more effective, tolerable, and affordable drugs. Objective. The present study is aimed at determining the in vivo antitrypanosomal effect of the hydromethanolic extracts of Solanum anguivi fruit extracts against the field isolates of T. congolense. Methods. The 80% methanol extracts of S. anguivi fruits were prepared by cold maceration technique. In vivo curative tests were done to check the effect of plant extract against T. congolense in Swiss albino mice. Plant extracts were administered at doses of 100, 200, and 400 mg/kg/body weight. Acute toxicity of the extracts at 2000 mg/kg was performed according to OECD guidelines. Data obtained from the experiment were analyzed using one-way ANOVA followed by Tukey test. Results. This study indicated that extract did not exhibit any sign of acute toxicity up to 2000 mg/kg/body weight. In curative test, extracts reduced parasitemia, preventing the drop in packed cell volume and body weight significantly ( p < 0.05 ), compared to control. Groups provided with the extract before infection got prolonged incubation period with chemoprophylactic effect at the doses of 100, 200, and 400 mg/kg. Phytochemical analysis showed presence of flavonoids, steroids, triterpens, saponins, glycosides, tannins, and alkaloids. Conclusion. The extract showed promising curative. Further effort is required to isolate and purify specific compounds responsible for antitrypanosomal activity of studied plant.

scholarly journals Acute Toxicity of Veterinary and Agricultural Formulations of Organophosphates Dichlorvos and Diazinon in Chicks

2011 ◽  
Vol 62 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Muna Al-Zubaidy ◽  
Yaareb Mousa ◽  
Mohammad Hasan ◽  
Fouad Mohammad
Keyword(s):  
Acute Toxicity ◽  
Toxic Action ◽  
Cholinesterase Inhibition ◽  
Plasma Samples ◽  
Brain Cholinesterase ◽  
Cholinesterase Activities ◽  
The Brain ◽  
Lethal Doses

Acute Toxicity of Veterinary and Agricultural Formulations of Organophosphates Dichlorvos and Diazinon in ChicksFormulation components of organophosphate insecticidal preparations might affect their toxic action in animals. The objective of this study was to examine and compare the acute toxicity and cholinesterase inhibition in seven to 14-day-old chicks dosed orally with dichlorvos and diazinon in standard veterinary and agricultural formulations. The acute (24 h) oral median lethal doses (LD50) of the formulations were determined using the up-and-down method. Respective LD50 of dichlorvos of the veterinary and agricultural formulations in chicks were 11.1 mg kg-1 and 6.51 mg kg-1 and those of diazinon 6.4 mg kg-1 and 6.7 mg kg-1. Plasma and brain cholinesterase activities were measured by electrometry after in vivo and in vitro exposure to organophosphates. The chicks showed signs of cholinergic toxicosis within one hour of dosing. Dichlorvos (8 mg kg-1) and diazinon (4 mg kg-1) in the veterinary and agricultural formulation significantly reduced both plasma and brain cholinesterase activities in the chicks. The veterinary formulation of dichlorvos reduced plasma ChE by 60 % and agricultural by 40 % and brain ChE by 93 % and 87 %, respectively. In contrast, ChE inhibition by diazinon in the agricultural formulation of diazinon was stronger than by the veterinary formulation; 72 % vs. 64 % in plasma and 97 % vs. 80 % in the brain, respectively. The highest in vitro inhibitions were observed with dichlorvos in the agricultural formulation (50 %) in the brain samples and with diazinon in the agricultural formulation (52 %) in the plasma samples. While they exist, differences between formulations cannot be taken as a rule and further investigations should inventory the toxicity of standard veterinary and agricultural organophosphate formulations in addition to the known data for pure forms.

Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI)

2020 ◽  
Vol 27 ◽  
Author(s):  
Leydianne Leite de Siqueira Patriota ◽  
Dayane Kelly Dias do Nascimento Santos ◽  
Bárbara Rafaela da Silva Barros ◽  
Lethícia Maria de Souza Aguiar ◽  
Yasmym Araújo Silva ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Trypsin Inhibitor ◽  
Hemolytic Activity ◽  
Moringa Oleifera ◽  
Biological Activities ◽  
Hematological Parameters ◽  
Behavioral Alterations ◽  
Female Mice

Background: Protease inhibitors have been isolated from plants and present several biological activities, including immunomod-ulatory action. Objective: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. Methods: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15–240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). Results: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15–30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as ΔΨm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. Conclusion: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

2018 ◽  
Vol 18 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Denis V. Mishchenko ◽  
Margarita E. Neganova ◽  
Elena N. Klimanova ◽  
Tatyana E. Sashenkova ◽  
Sergey G. Klochkov ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Toxicity ◽  
Histone Deacetylases ◽  
Hydroxamic Acids ◽  
Water Soluble ◽  
Male Rat ◽  
Hybrid Male ◽  
Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

In-vitro and in-vivo evaluation of antidiabetic activity of Withania coagulans extract

2019 ◽  
Vol 09 ◽  
Author(s):  
Tejas Patel ◽  
B.N. Suhagia
Keyword(s):  
Blood Glucose ◽  
Acute Toxicity ◽  
Aqueous Extract ◽  
Pancreatic Beta Cell ◽  
Toxicity Study ◽  
Acute Toxicity Study ◽  
Withania Coagulans ◽  
Study Results

Background: Diabetes mellitus is major issue to public health as its prevalence is rising day by day. Synthetic agents available for the diabetic treatment are expensive or produce undesirable side effect on chronic use and some of them are not suitable during pregnancy. Herbal medicines accepted widely due to side effects and low cost. Objective: The aim of present study was to evaluate the activity of Withania coagulans extract using In-vitro and In-vivo model. Methods: Different three types of Withania coagulans extract were prepared using aqueous (W1), Alcohol (W2) and hydro-alcoholic (50:50) mixture (W3). In-vitro Anti-diabetic activity of the all three extracts evaluated using RINm5F Pancreatic beta cells.Further, n-vivo anti-diabetic evaluation performed by administering 50 mg/kg (p.o) aqueous extract for 7 days in Streptozotocin (STZ)-induced mice. Body weight of the animals was also determined to perform acute toxicity study. Results: The results of in –vitro cell based study indicated that among all three extract, aqueous extract (W1) of Withania coagulans showed potential increase in inulin release. The EC50 of the W1 (249.6 µg/L) which is compared with standard (Glibenclamide) EC50. From the results of In-vitro study, W1 subjected for acute toxicity study and the acute toxicity study results indicated LD50 of 50mg/kg. Diabetic rats treated with W1 extract at oral dose of 50 mg/kg for 7 days showed 34.17% reduction in blood glucose in comparison to untreated diabetic (STZ-induced) rats. Blood glucose levels of Standard treated (Glibenclamide) and control untreated. Conclusion: In conclusion, results of pancreatic beta cell based study showed increase in insulin release by administration of extract. Further aqueous extract (W1) was potentially reduced blood glucose level in STZ induced diabetic mice.

Acute toxicity of C60–Cis-Pt nanocomplex in vivo

2021 ◽  
Author(s):  
Oksana Lynchak ◽  
Iryna Byelinska ◽  
Natalya Dziubenko ◽  
Halyna Kuznietsova ◽  
Olga Abramchuk ◽  
...  
Keyword(s):  
Acute Toxicity

scholarly journals Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 439
Author(s):  
Christopher G. Bunick ◽  
Jonette Keri ◽  
S. Ken Tanaka ◽  
Nika Furey ◽  
Giovanni Damiani ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Antibiotic Use ◽  
In Vivo Studies ◽  
Infection Model ◽  
Severe Acne ◽  
Rat Paw Edema ◽  
Infection And Inflammation

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.

scholarly journals In vitro and in vivo evaluation of virus-induced innate immunity in mouse

2021 ◽  
Vol 2 (3) ◽  
pp. 100708
Author(s):  
Long Shen ◽  
Xiao Shan ◽  
Penghui Hu ◽  
Yanan Zhang ◽  
Zemin Ji ◽  
...  
Keyword(s):  
Innate Immunity ◽  
In Vivo Evaluation
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