scholarly journals Single-Dose Toxicity Study on ML171, a Selective NOX1 Inhibitor, in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Se-Hyun Oh ◽  
Ji-Sun Ahn ◽  
Eun-Joo Oh ◽  
You-Jin Kim ◽  
Ju-Min Yook ◽  
...  
Keyword(s):  
Single Dose ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Anterior Lobe ◽  
Negative Control ◽  
Icr Mice ◽  
Injection Dose ◽  
Good Laboratory ◽  
Males And Females ◽  
Isoform Selectivity ◽  
Safe Dose

Background. ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. Methods. The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. Results. Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. Conclusion. Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.

TOKSISITAS AKUT INFUSA KULIT ARI KACANG TANAH (Arachis hypogea L.) PADA MENCIT BALB/ C

2018 ◽  
Vol 15 (2) ◽  
pp. 62
Author(s):  
Risha Fillah Fithria ◽  
Ririn Lispita Wulandari ◽  
Devi Nisa Hidayati ◽  
Lilis Rejeki
Keyword(s):  
Single Dose ◽  
Color Change ◽  
Negative Control ◽  
Control Group ◽  
Hair Color ◽  
Peanut Shell ◽  
Control Group Design ◽  
Safety Standards ◽  
Arachis Hypogea ◽  
Passive Behavior

ABSTRACTPeanut shell (PS) infusion has been shown to be antithrombocytopenia, but there has been no research on safety standards. This study aims to identify the symptoms of toxic effects, the potency of toxicity and histopathology of liver male Balb/C mice after a single dose of PS infusion. This research uses randomized matched posttest only control group design. Twenty five mice were divided into 5 orally dosage groups, ie, PS infusion with a dose of 0,026; 0.052; 0.104; 0.208 g/20gBW; and negative control of CMC Na 0.5%. The observation period is for 14 days. The results showed that single dose of PS infusion had a pseudo LD50 value ie > 0.208g/20gBW which was practically non toxic. Symptoms to watch out for the BW infusion were passive behavior, bradycnea, hair color change, hair loss, and weight loss at doses of 3 and 4. It is unclear whether liver damage ie inflammation, necrosis, and albuminous degeneration caused by PS infusion or other causes.keywords: acute toxicity, infusion, peanut shell

Liver preneoplastic changes in mice treated with the herbicide fomesafen

1999 ◽  
Vol 18 (5) ◽  
pp. 338-344 ◽  
Author(s):  
J Krijt ◽  
P Stránská ◽  
J Sanitraák ◽  
A Chlumská ◽  
F Fakan
Keyword(s):  
Single Dose ◽  
Single Injection ◽  
Diphenyl Ether ◽  
Liver Histology ◽  
Mouse Strains ◽  
Toxicological Evaluation ◽  
Liver Nodules ◽  
Icr Mice ◽  
Mice Liver ◽  
Foci Of Altered Hepatocytes

1 Effect of the diphenyl ether herbicide fomesafen on liver preneoplastic changes and porphyrin biosynthesis was examined in male C57BL/6J mice (0.23% in the diet for 14 months) and ICR mice (0.3% in the diet for 50 weeks). Fomesafen treatment resulted in preneoplastic changes (liver nodules and foci of altered hepatocytes) in both strains, uroporphyria developed only in ICR mice. 2 Iron pretreatment (600 mg/kg as a single dose) accelerated the development of fomesafen-induced preneoplastic changes in both mouse strains. The number of foci containing altered hepatocytes, as well as the number and size of liver nodules, were increased in iron-pretreated animals. 3 A single injection of iron induced marked uroporphyria in C57BL/6J mice after 14 months (liver porphyrin content 102 nmol/g). This uroporphyria was further potentiated by fomesafen administration (208 nmol/g). 4 In ICR mice, liver histology was apparently normal after a 3 month recovery from fomesafen treatment (0.32% for 9 months). Liver porphyrin content (260 nmol/g) started to decrease immediately after fomesafen withdrawal, but was still significantly elevated after 3 months (5 nmol/g), as compared to controls (1 nmol/g). 5 It is concluded that the toxicological evaluation of fomesafen should focus on liver porphyrin biosynthesis.

scholarly journals Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anita E Autry ◽  
Zheng Wu ◽  
Vikrant Kapoor ◽  
Johannes Kohl ◽  
Dhananjay Bambah-Mukku ◽  
...  
Keyword(s):  
Positive Control ◽  
Negative Control ◽  
Neural Pathways ◽  
Axon Terminals ◽  
Health And Disease ◽  
Circuit Component ◽  
Urocortin 3 ◽  
Males And Females ◽  
New Framework

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion, and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.

scholarly journals Glutathione reductase deficiency in Saudi Arabia

1999 ◽  
Vol 5 (6) ◽  
pp. 1208-1212
Author(s):  
A. S. Warsy ◽  
M. A. El Hazmi
Keyword(s):  
Glutathione Reductase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Normal Functioning ◽  
Riboflavin Deficiency ◽  
Males And Females ◽  
Presence And Absence ◽  
Glutathione Reductase Deficiency ◽  
The Stability ◽  
Riboflavin Deficient ◽  
Reduced Nicotinamide Adenine Dinucleotide

Glutathione reductase [GR]is a ubiquitous enzyme required for the conversion of oxidized glutathione [GSSG] to reduced glutathione [GSH] concomitantly oxidizing reduced nicotinamide adenine dinucleotide phosphate [NADPH]in a reaction essential for the stability and integrity of red cells. Mutations in the GR gene and nutritional deficiency of riboflavin, a co-factor required for the normal functioning of GR, can cause GR deficiency. We conducted a study on 1691 Saudi individuals to determine the overall frequency of GR deficiency and to identify whether the deficiency results from genetic or acquired causes or both. The activity of GR was measured in freshly prepared red cell haemolysate in the presence and absence of flavin adenine dinucleotide [FAD]and the activity coefficient [AC] was determined. Samples with low GR activity [>2.0 IU/g haemoglobin] both in the presence and absence of FAD and an AC between 0.9 and 1.2 were considered GR-deficient. Samples with AC >/= 1.3 were considered riboflavin-deficient. The overall frequency of partial GR deficiency was 24.5% and 20.3% in males and females respectively. In addition, 17.8% of males and 22.4% of females suffered from GR deficiency due to riboflavin deficiency. This could be easily corrected by dietary supplementation with riboflavin. No cases of severe GR deficiency were identified

Metabolic programming in offspring of mice fed fructose during pregnancy and lactation

2021 ◽  
pp. 1-14
Author(s):  
Marina Lummertz Magenis ◽  
Adriani Paganini Damiani ◽  
Gustavo de Bem Silveira ◽  
Ligia Salvan Dagostin ◽  
Pamela Souza de Marcos ◽  
...  
Keyword(s):  
Fatty Liver Disease ◽  
Negative Control ◽  
Nitrite Concentration ◽  
Male And Female ◽  
Nonalcoholic Fatty Liver ◽  
Biochemical Effects ◽  
High Consumption ◽  
Pregnancy And Lactation ◽  
Males And Females ◽  
And Oxidative Stress

Abstract Fructose (C6H12O6), also known as levulose, is a hexose. Chronic consumption of fructose may be associated with increased intrahepatic fat concentration and the development of insulin resistance as well as an increase in the prevalence of nonalcoholic fatty liver disease and hyperlipidemia during pregnancy. Despite the existence of many studies regarding the consumption of fructose in pregnancy, its effects on fetuses have not yet been fully elucidated. Therefore, the objective of this study was to evaluate the genetic and biochemical effects in offspring (male and female) of female mice treated with fructose during pregnancy and lactation. Pairs of 60-day-old Swiss mice were used and divided into three groups; negative control and fructose, 10%/l and 20%/l doses of fructose groups. After offspring birth, the animals were divided into six groups: P1 and P2 (males and females), water; P3 and P4 (males and females) fructose 10%/l; and P5 and P6 (males and females) fructose 20%/l. At 30 days of age, the animals were euthanized for genetic and biochemical assessments. Female and male offspring from both dosage groups demonstrated genotoxicity (evaluated through comet assay) and oxidative stress (evaluated through nitrite concentration, sulfhydril content and superoxide dismutase activity) in peripheral and brain tissues. In addition, they showed nutritional and metabolic changes due to the increase in food consumption, hyperglycemia, hyperlipidemia, and metabolic syndrome. Therefore, it is suggested that high consumption of fructose by pregnant female is harmful to their offspring. Thus, it is important to carry out further studies and make pregnant women aware of excessive fructose consumption during this period.

Single-dose acute toxicity of intraperitoneally administered Vital-Shoot containing reduced glutathione in ICR mice

2017 ◽  
Vol 41 (3) ◽  
pp. 133-136
Author(s):  
Chun-Nam Cha ◽  
◽  
Eun-Kee Park ◽  
Chang-Yeul Yoo ◽  
Suk Kim ◽  
...  
Keyword(s):  
Single Dose ◽  
Acute Toxicity ◽  
Reduced Glutathione ◽  
Icr Mice

scholarly journals Comparison of single-dose cefuroxime axetil with ciprofloxacin in treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing Neisseria gonorrhoeae strains.

1996 ◽  
Vol 40 (12) ◽  
pp. 2775-2780 ◽  
Author(s):  
E M Thorpe ◽  
J R Schwebke ◽  
E W Hook ◽  
A Rompalo ◽  
W M McCormack ◽  
...  
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Confidence Interval ◽  
Neisseria Gonorrhoeae ◽  
Single Oral Dose ◽  
Cefuroxime Axetil ◽  
Female Patients ◽  
Male Patients ◽  
Males And Females ◽  
Uncomplicated Gonorrhea

A randomized, multicenter, investigator-blind trial was conducted to compare the efficacies of cefuroxime axetil and ciprofloxacin for treatment of patients with uncomplicated gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae (PPNG). A total of 832 patients (434 females and 398 males) received a single oral dose of cefuroxime axetil (1,000 mg [417 patients]) or ciprofloxacin (500 mg [415 patients]). N. gonorrhoeae was eradicated from the cervix in 114 of 118 (97%) and 118 of 119 (99%) bacteriologically evaluable females treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.213; difference, -2%; 95% confidence interval, -6 to 1%), and from the urethra in 154 of 166 (93%) and 171 of 171 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P < 0.001; difference, -7%; 95% confidence interval, -11 to -3%). Both treatments were effective in eradicating N. gonorrhoeae in females with rectal infections (cefuroxime axetil, 29 of 30 [97%]; ciprofloxacin, 25 of 25 [100%]; P = 1.00). In small numbers of patients, cefuroxime axetil was less effective than ciprofloxacin in treating males with pharyngeal infections (eradication in 4 of 10 and in 8 of 8 patients, respectively; P = 0.013). PPNG was eradicated from the cervix in 22 of 23 (96%) and 32 of 32 (100%) bacteriologically evaluable female patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.418; difference, -4%; 95% confidence interval, -13 to 4%), and from the urethra in 35 of 36 (97%) and 34 of 34 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 1.00; difference, -3%; 95% confidence interval, -8 to 3%). The incidences of drug-related adverse events were similar for the two study drugs. In summary, treatment with a single oral dose of cefuroxime axetil is as effective as treatment with a single oral dose of ciprofloxacin in eradicating PPNG from males and females with uncomplicated gonorrhea (urethral and endocervical), and both regimens are well-tolerated. However, in the present study, cefuroxime axetil was less effective than ciprofloxacin in treating urethral gonococcal infections in male patients, although both study drugs were highly effective in treating cervical gonococcal infections in female patients.

Effects of the anthelmintics clorsulon, rafoxanide, mebendazole and arprinocid on Echinostoma caproni in ICR mice

1995 ◽  
Vol 69 (4) ◽  
pp. 373-374 ◽  
Author(s):  
K. Maurer ◽  
M. Decere ◽  
B. Fried
Keyword(s):  
Single Dose ◽  
New Jersey ◽  
Polyethylene Glycol ◽  
Not Given ◽  
Stomach Tube ◽  
Echinostoma Caproni ◽  
Post Exposure ◽  
Icr Mice

AbstractFemale ICR mice, 5 to 6 weeks old, were exposed by stomach tube to 25 metacercarial cysts of Echinostoma caproni per mouse. At 14 days post-exposure, mice were fed by stomach tube clorsulon (1000 mg/kg, 25 mg/kg, 500 mg/kg and 100 mg/kg) or rafoxanide (50 mg/kg, 25 mg/kg and 5 mg/kg) dissolved in dimethy lsulphoxide (DMSO) carrier and mebendazole (1000mg/kg and 500 mg/kg) or arprinocid (100 mg/kg and 50 mg/kg) suspended in a2:1 polyethylene glycol (PEG)/DMSO carrier. All drugs were obtained from Meerck In. (Rahway, New Jersey, USA) and only single dose regimes were used. Experimentally infected mice that served as controls received either DMSO or 2:1 PEG/DMSO carriers or were not given the carrier. Mice were necropsied 15v, 16, 18 and 20 days post-exposure to worms. Doses of 100 mg/kg of clorsulon and 50 mg/kg of rafoxanide were 100% effective in eliminating the echinostomes on day 1 post-administration of the anthelmintics. Mebendazole and arprinocid were ineffection in eliminating worms at 1 or 2 days post drug daministration.

scholarly journals Porvac® Subunit Vaccine E2-CD154 Induces Remarkable Rapid Protection against Classical Swine Fever Virus

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 167
Author(s):  
Yusmel Sordo-Puga ◽  
Marisela Suárez-Pedroso ◽  
Paula Naranjo-Valdéz ◽  
Danny Pérez-Pérez ◽  
Elaine Santana-Rodríguez ◽  
...  
Keyword(s):  
Single Dose ◽  
Classical Swine Fever Virus ◽  
Subunit Vaccine ◽  
Classical Swine Fever ◽  
Negative Control ◽  
Fever Virus ◽  
Protein Vaccine ◽  
Post Vaccination ◽  
Unvaccinated Control ◽  
A Subunit

Live attenuated C-strain classical swine fever vaccines provide early onset protection. These vaccines confer effective protection against the disease at 5–7 days post-vaccination. It was previously reported that intramuscular administration of the Porvac® vaccine protects against highly virulent classical swine fever virus (CSFV) “Margarita” strain as early as seven days post-vaccination. In order to identify how rapidly protection against CSFV is conferred after a single dose of the Porvac® subunit vaccine E2-CD154, 15 swine, vaccinated with a single dose of Porvac®, were challenged intranasally at five, three, and one day post-vaccination with 2 × 103 LD50 of the highly pathogenic Cuban “Margarita” strain of the classical swine fever virus. Another five animals were the negative control of the experiment. The results provided clinical and virological data confirming protection at five days post-vaccination. Classical swine fever (CSF)-specific IFNγ T cell responses were detected in vaccinated animals but not detected in unvaccinated control animals. These results provided the first data that a subunit protein vaccine demonstrates clinical and viral protection at five days post-vaccination, as modified live vaccines.

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