Study of the Acute Toxicity of a New Dosage Form of Naloxone Hydrochloride for Intranasal Administration

AbstractThe experiment was conducted on 10 Wistar rats, male and female, with initial body weight 270–280 g (males) and 250–260 g (females). The drug was administered using a spray cap in 10 doses of 0.1 mg at 45 min intervals. The average cumulative dose of the drug per naloxone hydrochloride was 36.6 mg/kg for males and 39.4 mg/kg for females. The animals were monitored for 2 weeks after the exposure and then euthanized by a gentle decapitation.We noticed that after each drug administration the animals showed a decrease in motor activity. During the observation period there were no animal deaths or signs of abnormalities in their general state or behavior. Beginning on day 7 a significant increase in body weight of the animals was noted in comparison with the initial data. The relative mass of the internal organs of the treated rats remained within the physiological norm.We conclude that naloxone hydrochloride after an intranasal administration at 36.6 mg/kg for males and 39.4 mg/kg for females does not cause death of animals and or have a toxic effect on their general state, does not change their protein metabolism characteristics or the appearance of the internal organs and their mass.

Download Full-text

PSVII-8 Equations for prediction of empty body weight of water buffaloes finished in feedlot

Journal of Animal Science ◽

10.1093/jas/skaa278.546 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 305-306

Author(s):

Andre M Jorge ◽

Caroline L Francisco ◽

André M Castilhos ◽

Matheus Henrique P Martins Narciso ◽

Amanna G Jacaúna ◽

...

Keyword(s):

Body Weight ◽

Prediction Equation ◽

Adaptation Period ◽

Initial Body Weight ◽

Internal Organs ◽

Animal Blood ◽

Water Buffaloes ◽

Genetic Groups ◽

Ad Libitum ◽

General Prediction

Abstract This study aimed to develop equations to predict the empty body weight (EBW) using the shrunk body weight (SBW) of water buffaloes of three genetic groups (GG:Jafarabadi, Mediterranean, and Murrah; n = 65 for each GG), considering possible variations among GG. One-hundred-ninety-five non-castrated males (390±32 days of age; 327±51.96 kg of initial body weight - BW) from two years of similar experiments were used. Animals of each GG were allocated in collective pens for 28 days of adaptation period. Diet and water were offered ad libitum. Animal SBW were recorded at the beginning and every 28 days until the averages SBW reached the values determined (420, 480, and 540kg of SBW). After slaughter and to obtain the EBW, the non-carcass components of each animal [blood, paws, head, leather, tail, gastrointestinal tract (GIT), liver, kidneys, internal fat, and other internal organs] were weighed. The full GIT of each animal was weighed to obtain the total weight, and then emptied, washed, drained, and weighed to obtain the weight of the GIT content. Initially, data were analyzed using UNIVARIATE procedure in SAS. SBW recorded prior to slaughter were categorized according to SBW proposed considering the coefficient of variation below 10% for each GG to increase the precision of the data used, which decreased the initial n to 104 animals. Equations were developed and tested for GG effect using GLM and REG procedures in SAS. Tendency of GG effect was detected (P = 0.06). Thus, different prediction equations were determined for each GG, and a general prediction equation was developed for the three GG (Table 1). In conclusion, the results suggest it is possible to use distinct equations to predict the EBW according to GG as well as a general equation can be also used, resulting in high predictions of EBW of water buffaloes finished in feedlot.

Download Full-text

Pharmacokinetics in the human of a new synthetic vasopressin and oxytocin uterine antagonist

Acta Endocrinologica ◽

10.1530/acta.0.1120465 ◽

1986 ◽

Vol 112 (4) ◽

pp. 465-472 ◽

Cited By ~ 19

Author(s):

Stefan Lundin ◽

Mats Åkerlund ◽

Per-Olof Fagerström ◽

Arnar Hauksson ◽

Per Melin

Keyword(s):

Body Weight ◽

Half Life ◽

Intranasal Administration ◽

Bolus Injection ◽

Total Body Clearance ◽

Late Pregnancy ◽

Primary Dysmenorrhoea ◽

Total Body ◽

Observation Period ◽

Body Clearance

Abstract. The pharmacokinetics in the human of 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin (dE-TVT), was studied after iv and intranasal administration in 11 subjects at 12 experiments each route. The plasma concentration of the analogue was analysed by means of an arginine vasopressin antibody, which cross-reacted with dE-TVT to 4.7%. When given intravenously as bolus injection (10 nmol/kg/body weight), the total body clearance amounted to 0.623 ± 0.099 (sem) 1/h kg and the half-life to 16.2 ± 2.4 min. After intranasal administration (100 nmol/kg/body weight), the bioavailability was 10.5 ± 2.9%. Peak concentrations in plasma appeared 2–8 min after iv and 10–45 min after intranasal administration. At the end of an observation period of 2 h measurable amounts in plasma were still found in one of the iv and seven of the intranasal experiments. It is concluded that the moderately long half-life is suitable for the treatment of hospitalized patients in premature labour where promising results with intravenous infusion (50 μg/min) of dE-TVT have been obtained. It is still uncertain whether or not the absorption of dE-TVT is sufficient for intranasal administration to out-patients with uterine hyperactivity in late pregnancy and to patients with primary dysmenorrhoea, where significant relief of symptoms were seen after iv administration (10 μg/kg body weight).

Download Full-text

Research of acute toxicity of the drug HEXIA

Farmatsevtychnyi zhurnal ◽

10.32352/0367-3057.6.16.06 ◽

2018 ◽

pp. 88-94

Author(s):

V. L. Karbovskyy ◽

I. A. Shevchuk ◽

O. V. Kurkina ◽

T. Ye. Makovska

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Daily Basis ◽

Relative Mass ◽

Intragastric Administration ◽

Internal Organs ◽

Laboratory Rats ◽

Rats And Mice ◽

The Impact ◽

Female Laboratory

Diseases of the genitourinary system caused by pathogenic and potentially pathogenic microorganisms, which result into disbiosis of urinary organs, remain an urgent problem of dermatovenereology, gynecology and urology, despite the fact that there is a significant number of available and new medicines to treat them. The aim of the work was to determine the safety of the preparation Hexia within experiments on animals. The acute toxicity of Hexia has been determined on 20 adult female laboratory rats under the conditions of hourly intravaginal administration of the preparation with a dose of 70 mg/kg during 12 hours, as well as on 20 female laboratory rats and 20 female laboratory mice with a single intragastric administration in a dose of 145 mg/kg. The assessment of the impact of the preparation studied was performed on the basis of the following parameters: a) mortality (terms of death of animals in each group, on a daily basis); b) assessment of toxicity development (on a daily basis), including an assessment of the visual environment of the area of injection (the presence of irritation, redness, edema); c) dynamics of body weight changes (in the initial state, on the 4th, 7th and 14th day after application); d) macroscopy of internal organs, mass coefficients of internal organs within rats (on the 14th day). It has been found that intravaginal application and a single intragastric administration of the preparation Hexia in the form of pessaries, which contain chlorhexidine digluconate, does not result into death of rats and mice, brings no effect on body weight gain, integrative parameters of the functional state of laboratory animals as well as on the relative mass of internal organs, which implies the absence of significant toxic effect of the preparation. Thus, the results of the studies conducted indicate that the median lethal dose for Hexia in case of intravaginal application to rats or intragastric administration to rats and mice is beyond the rate of 500 mg/kg. According to the toxicological classification of substances Hexia belongs to the IV class of toxicity – low toxic substances.

Download Full-text

Hypoglycemic effect of alloxan and thymulin both diluted in wistars rats with degeneration of beta cells islets of Langerhans

International Journal of High Dilution Research - ISSN 1982-6206 ◽

10.51910/ijhdr.v11i40.579 ◽

2021 ◽

Vol 11 (40) ◽

pp. 184-184

Author(s):

Ruggero Zalla Neto ◽

Patricia Moriguchi ◽

Aline Fernando Rodrigues Chaves ◽

Ingrid Lauren Brites de Oliveira

Keyword(s):

Diabetes Mellitus ◽

Body Weight ◽

Beta Cells ◽

Clinical Improvement ◽

Feed Intake ◽

Wistar Rats ◽

Experimental Diabetes ◽

General State ◽

Male Wistar Rats ◽

Biological Tests

Diabetic animals induced by alloxan show severe hyperglycemia and intense catabolism characterized by the absence of insulin. Therefore, the objective of this study is to assess whether the alloxan 6CH, is able to reverse or mitigate the changes promoted by diabetes mellitus, as well as assess the effects of thymulin. In biological tests male Wistar rats were used induced to experimental diabetes by the administration of alloxan (iv 42 mg / kg). The sample comprised four groups (n = 4): G1 ÃƒÂ¢Ã¢â€šÂ¬Ã¢â‚¬Å“ control without the induction of diabetes, G2 - diabetic without treatment, G3 - diabetic treated with thymulin 12CH and G4 - treated with alloxan 6CH. The data were statistically analyzed by ANOVA followed by Tukey-Kramer test (p < 0.05). After treatment for 40 days slight decrease of glucose in animals treated with alloxan (502 Ãƒâ€šÃ‚Â± 28) mg/dl and thymulin (500 Ãƒâ€šÃ‚Â± 10) mg/dl was observed compared with untreated animals (563 Ãƒâ€šÃ‚Â± 23)mg/dl. Remained unchanged feed intake and water, however, significant decrease of body weight in diabetic group (96 Ãƒâ€šÃ‚Â± 21)g was observed compared to animals treated with alloxan (27 Ãƒâ€šÃ‚Â± 23)g and thymulin (20 Ãƒâ€šÃ‚Â± 16)g, fact not observed when the last two groups are compared with the control (5.1 Ãƒâ€šÃ‚Â± 3.9)g. Significant reduction in the percentage of lymphocytes in diabetic animals (44.8 Ãƒâ€šÃ‚Â± 2.4)% and increase in the group treated with thymulin (12CH) (83.3 Ãƒâ€šÃ‚Â± 4.5)% was checked, when compared to the others. Animals treated with alloxan and thymulin showed clinical improvement. Based on these findings it is concluded that alloxan and thymulin improve the general state of the animal, and suggest inhibition of strong catabolism observed in diabetic animals without treatment.

Download Full-text

Impact of polyvinyl chloride, polystyrene, and polyethylene on the organism of mice

Regulatory Mechanisms in Biosystems ◽

10.15421/021908 ◽

2019 ◽

Vol 10 (1) ◽

pp. 50-55 ◽

Cited By ~ 3

Author(s):

M. A. Lieshchova ◽

V. V. Brygadyrenko ◽

N. M. Tishkina ◽

P. M. Gavrilin ◽

A. A. Bohomaz

Keyword(s):

Body Weight ◽

Toxic Effect ◽

Polyvinyl Chloride ◽

The Body ◽

Laboratory Animals ◽

Relative Mass ◽

Internal Organs ◽

Peripheral Organs ◽

Group I ◽

The Impact

Goods of plastic, due to their durability, universality and economical properties are broadly used in all spheres of life. On the whole, polymers are inert and nontoxic, but in the process of their production, various additives are used, which on contact or introduction into an organism has a negative effect on it. In our study, we determined the impact of some types of plastic (polyvinyl chloride, polysterene and polyethylene) on the organism of laboratory animals according to changes in their body weight, indices of mass of the internal organs, and blood parameters. For the experiment, we formed four groups of white male mice at the age of 3 weeks and average body weight of 50 g. For each group, we used different litter. For group I, the litter was sawdust; and for the other groups we added plastic products in different volumes to the sawdust; for group II finely cut polyvinyl chloride, for group III cut polyethylene, and for group IV granules of polystyrene. Every 3 days, we determined the body weight of the animals, and 32 days later we determined mass of the organs, clinical and biochemical parameters of the blood. Addition of polyvinyl chloride, polyethylene, and polystyrene into the substrate for mice did not have a significant effect on tempi of growth of body weight, and also relative mass of heart and lungs. Polyvinyl chloride and polystyrene have an immune-suppressive effect, and polyvinyl chloride affects both central and peripheral organs, and polystyrene mostly harms the peripheral organs. All used types of plastic cause leukocytopenia, following which neutrophilia of band neutrophils and monocytosis takes place as a result of damage to the biological barriers. We determined the systemic toxic effect of the studied types of plastic on the internal organs, which manifested in increase in their mass (liver, kidneys), steep increase in the activity of liver enzymes (AST, ALT), simultaneous decrease in activity of alkaline phosphatase and content of cholysterol and glucose in the blood serum of the mice. Also polyvinyl chlorine, polyethylene and polystyrene cause degeneration of the epithelium of the uriniferous tubule, which is manifested in reduction of globulins and creatinine in the blood of animals from the experimental groups following increase in relative mass of the kidneys. The results of our research allow us to state that different types of plastic can cause toxic effect on animals, as well as people who are in frequent contact with them.

Download Full-text

Prediction of body weight and composition in lactating dairy cows: Prediction of crude protein contents in internal organs

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200010929 ◽

2005 ◽

Vol 2005 ◽

pp. 181-181

Author(s):

T. Yan ◽

R. E. Agnew

Keyword(s):

Body Weight ◽

Dairy Cows ◽

Protein Metabolism ◽

Crude Protein ◽

Farm Animals ◽

Accurate Estimation ◽

Internal Organs ◽

Live Animal ◽

Body Protein ◽

Lactating Dairy Cows

Heat production of animals is mainly derived from body protein metabolism and energy expenditure per unit protein in internal organs is much higher than skeletal muscle. The accurate estimation of CP mass in internal organs can thus improve rationing systems for farm animals. The objective of the present study was to examine relationships between CP mass in internal organs and empty body weight (EBW) with other live animal variables in lactating dairy cows.

Download Full-text

Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0365 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Elvine P. Nguelefack-Mbuyo ◽

Fernande P. Peyembouo ◽

Christian K. Fofié ◽

Télesphore B. Nguelefack

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Catalase Activity ◽

Wistar Rats ◽

Chronic Treatment ◽

Body Weight Loss ◽

Redox Status ◽

Duration Of Treatment ◽

Renal Hypertrophy ◽

Subchronic Treatment

Abstract Objectives Dexamethasone is used experimentally to induce insulin resistance and type 2 diabetes. However, data concerning the dose, the duration of treatment, and the associated comorbidities are inconsistent. The aim of this study was to compare the effects of different doses of dexamethasone and the duration of treatment necessary for the development of a model of insulin resistance that mimics the clinical condition with the associated comorbidities. Methods Dexamethasone was administered intramuscularly to male Wistar rats, at doses of 500 and 1,000 µg/kg/day for the subchronic treatment (eight consecutive days) and at doses of 5, 25, 50, and 100 µg/kg/day in chronic treatment (28 consecutive days). Effects on body weight, metabolism, hemodynamics, renal function, and redox status were evaluated. Results Both treatments induced a progressive body weight loss that was drastic in subchronic treatment, improved glucose tolerance without affecting fasting glycemia. Doses of 1,000 and 100 µg/kg were associated with hypertriglyceridemia, hypertension, and increased heart rate, cardiac and renal hypertrophy. Increased creatinemia associated with reduced creatinuria were observed in sub-chronic treatment while increased proteinuria and reduced creatinuria were noticed in chronic treatment. 1,000 µg/kg dexamethasone caused an increase in hepatic, and renal malondialdehyde (MDA) and glutathione (GSH) coupled with a reduction in catalase activity. The dose of 100 µg/kg induced a rise in GSH and catalase activity but reduced MDA levels in the kidney. Conclusions Doses of 1,000 µg/kg for subchronic and 100 µg/kg for chronic treatment exhibited similar effects and are the best doses to respective time frames to induce the model.

Download Full-text