scholarly journals Acute and Long-Term Toxicity of Mango Leaves Extract in Mice and Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Zhang ◽  
Jian Li ◽  
Zhizhen Wu ◽  
Erwei Liu ◽  
Pingping Shi ◽  
...  
Keyword(s):  
Body Weight ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Maximal Dose ◽  
Sd Rats ◽  
Body Weight Increase ◽  
Mango Leaves ◽  
Long Term Studies

The acute toxicity of mango leaves extract (MLE) at the maximal dose (18.4 g/kg) was studied in ICR mice and no abnormalities were detected during the experiment. The long-term studies at various doses of MLE (100 mg/kg, 300 mg/kg, and 900 mg/kg) in SD rats for 3 consecutive months revealed that, compared with the control group, rats in MLE treated groups showed slight body weight increase and higher fat weight; the serum TG and CHOL levels and the epididymis weight of male rats were a little higher; the serum K+level of female rats was on the low side but the weights of liver, kidney, and adrenal gland were on the high side. In addition to this, no other obvious abnormalities were detected.

scholarly journals Study on optimization and stability of a single dose streptozotocin-induced diabetic modeling in rats

2020 ◽  
Author(s):  
Yao Zhang ◽  
jiao Zhang ◽  
Ming Hong ◽  
Jingyi Huang ◽  
Rui Wang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sd Rats ◽  
Male And Female Rats

Abstract BackgroundOptimization of experimental conditions in streptozotocin induced diabetic model in Sprague Dawley (SD) rats to evaluate the stability of the model.MethodsMale and female SD rats were randomly divided into control group, STZ 45 group (STZ: 45 mg / kg), STZ 65 group (STZ: 65 mg / kg), STZ 85 group (STZ: 85 mg / kg), high fat diet with STZ 45 group (STZ: 45 mg / kg), high fat diet with STZ 65 group (STZ: 65 mg / kg), high fat diet with STZ 85 group (STZ: 85 mg / kg). N = 6 in each group. The changes of body weight and blood glucose were observed dynamically.ResultsThere was no significant difference in blood glucose or body weight between the STZ 45 group and the control group in both male and female rats, whether or not they were on a high-fat diet. However, there were significant differences in blood glucose between the high-dose STZ group and the control group in both male and female rats, regardless of whether the rats were on a high-fat diet or not (P < 0.05 or P < 0.01). Compared with the control group, there were significant differences in blood glucose levels (P < 0.05 or P < 0.01) and higher blood glucose levels in the male rats fed with the normal diet than that in those fed with the high-fat diet.ConclusionsIn this study, male rats fed with ordinary feed and injected STZ dose of 65 mg / kg were the most stable and ideal diabetic rat.

THE INTERRELATION OF THE GROWTH AND METABOLIC RESPONSES TO ANTERIOR PITUITARY GROWTH HORMONE ADMINISTRATION

1957 ◽  
Vol 35 (1) ◽  
pp. 1113-1118
Author(s):  
George H. Beaton ◽  
Hannah Z. Banky ◽  
Audrey M. Haufschild
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Amino Nitrogen ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Weight Increase ◽  
Metabolic Alterations ◽  
Nitrogen Levels ◽  
Body Weight Increase

Doses of growth hormone which were minimal with respect to body weight increase were sufficient to produce significant alterations in liver alanine – glutamic transaminase and arginase activities and blood urea and amino nitrogen levels. The biochemical effects of the hormone appeared coincident with the body weight increase. Female rats showed a more pronounced response to growth hormone than did male rats. This sex difference was evident with respect to all of the metabolic alterations observed. Although it is not possible to state whether the metabolic alterations are direct effects of the hormone, they do take an integral part in bringing about the over-all biological effect.

scholarly journals Long-term sucrose-drinking causes increased body weight and glucose intolerance in normal male rats

2005 ◽  
Vol 93 (5) ◽  
pp. 613-618 ◽  
Author(s):  
Takahiro Kawasaki ◽  
Akiko Kashiwabara ◽  
Tadashi Sakai ◽  
Kanji Igarashi ◽  
Nobuyuki Ogata ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Intolerance ◽  
Plasma Glucose ◽  
Male Rats ◽  
Control Group ◽  
Normal Male ◽  
Oral Glucose ◽  
Old Rats ◽  
Sucrose Drinking

The current epidemic of diabetes likely reflects marked changes in environmental factors, although genetic susceptibility plays a powerful role in the occurrence of diabetes in certain populations. We investigated whether long-term sucrose-drinking causes hyperglycaemia in male Wistar-Imamichi littermates (n 32), which are not genetically susceptible to diabetes or obesity. Each litter was divided equivalently into two groups, the sucrose group and the control group. The sucrose group received 300 g/l sucrose water and the control group received regular water until 42 weeks of age. Rats were weighed every 1 or 2 weeks. Oral glucose tolerance tests were performed at 28 and 36 weeks of age. Plasma glucose and insulin concentrations were measured. Body weights were significantly greater in the sucrose group than in the control group in 18-week-old rats (P<0·05), and the difference between the two groups reached 163 g by the end of the study (P<0·01). The 120 min post-load plasma glucose concentration in the sucrose group was 11·4 (sd 2·8) mmol/l in 28-week-old rats and 12·7 (sd 2·2) mmol/l in 36-week-old rats, while that of the control group remained approximately 7·3–7·7 mmol/l. In the sucrose group, the plasma insulin peak occurred 30 min post-load at 28 weeks of age; but the peak disappeared and hyperinsulinaemia was prolonged at 36 weeks of age. In conclusion, long-term sucrose-drinking causes increased body weight and glucose intolerance in normal male rats.

scholarly journals The subchronic toxic effects of Mosla Chinensis Maxim in normal rats.

2020 ◽  
Author(s):  
Dan Lei ◽  
Longxue Li ◽  
Shenghong Huang ◽  
Li Liu ◽  
Pingdong Cai ◽  
...  
Keyword(s):  
Dose Group ◽  
Intestinal Flora ◽  
Female Rats ◽  
Toxic Effects ◽  
Fixed Dose ◽  
Control Group ◽  
Subchronic Toxicity ◽  
Male And Female ◽  
Sd Rats

Abstract Background: The aim of this work was to study the toxic effects and target organs of Mosla Chinensis Maxim (MCM) in rats and provide theoretical basis for clinical medication.Methods: The subchronic toxicity study was conducted on 60 male and female SD rats using the fixed-dose method for the treatment group and 20 male and female SD rats for the control. At the subchronic toxicity study, the water extract of MCM with fixed-dose of 0.2g/kg/day, 2g/kg/day and 20g/kg/day was administered for 90 days intragastric, and the control group was given the same amount of distilled water. After 90 days, the general conditions of the rats were observed. Assesment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occured in gut flora and urine metabolism. Results: The results showed that there were no significant toxic effects observed at all doses on physical sign and reactivity and fecal property of rats in the treatment groups had no obvious difference from those in control group. The results of routine blood test showed that the number of red blood cells in the male medium dose group and the female low dose group were significantly different from those in the control group (P<0.05). The results of serum biochemical indicators test showed that MCM had influence on the indicators of liver and kidney function, but it had no toxicological significance. In terms of glucose and lipid metabolism, the LDL level of male rats was lower than that of the control group (P<0.05). Compared with the control group, GLU level of female rats in the low, medium and high dose groups was significantly increased (P<0.05), indicating that long-term administration of MCM would affect the glucose level of female rats. The results of intestinal flora diversity showed that feeding MCM for 90 days had an impact on the distribution of intestinal flora. The content of lactobacillus increased and the ratio of Firmicutes and Bacteroidetes (F/B) was also affected, but there was no significant difference. Conclusions: These findings showed that the long-term intragastric administration of the MCM is safe to use within its dose recommendation. But it could have slight affect the metabolism of uric acid by changing the composition of intestinal flora and affecting the metabolism of tryptophan.

scholarly journals The toxicity of the technical product, derived triazolinones

2020 ◽  
Vol 64 (2) ◽  
pp. 83-87 ◽  
Author(s):  
Valery N. Rakitskii ◽  
E.G. Chkhvirkiya ◽  
T.M. Epishina
Keyword(s):  
Body Weight ◽  
Hematological Parameters ◽  
Oral Intake ◽  
Total Activity ◽  
The Body ◽  
Male Rats ◽  
Control Group ◽  
Long Term Effects ◽  
Technical Product

Introduction. Technical products that are part of pesticides recommended for use in agriculture must undergo a comprehensive sanitary and Toxicological examination, which is the basis for preventing the adverse effects of pesticides on the health of workers and the population, as well as on the sanitary state of the environment. Purpose of research - the study of the biological effect of the technical product derived triazolinthionov, with its repeated oral intake in mammals (rats), justification of the permissible daily dose (DSD) for humans. Material and methods. Chronic (12 months) experiment was conducted on male rats with a body weight of 200-210 g tested doses: 5.0; 50.0 and 500.0 mg/kg body weight (1 control and 3 experimental groups and 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water and food consumption, fixed the timing of death, recorded changes in body weight, physiological, biochemical and hematological parameters. Results. It was found that the dose of 5.0 mg/kg body weight does not cause significant changes in all studied parameters, doses of 50.0 and 500.0 mg/kg body weight had a polytropic effect on the body of experimental animals. Discussion. The studied technical product at repeated intake in doses of 50,0 and 500,0 mg/kg of body weight causes changes in the state of the Central nervous system of animals (statistically significant changes in SPP, total activity, path length, rest time), as well as changes in carbohydrate, lipid, and lipoprotein metabolism in the body, as evidenced by statistically significant changes in biochemical and hematological indicators. Consequently, doses of 50,0 and 500,0 mg/kg of body weight have a polytropic effect on the body of male rats and are effective. The dose of 5.0 mg/kg of body weight, when administered in animals of the experimental group in comparison with animals of the control group, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. On the basis of an inactive dose of 5.0 mg/kg of body weight and a reserve factor of 100, we have scientifically justified DSD for humans at the level of 0.05 mg/kg. Conclusion. Studies have shown that long-term repeated oral administration of the studied product into the body of animals (male rats) at a dose of 5.0 mg per 1 kg of body weight does not cause statistically significant changes in all the studied parameters, so the indicated dose is invalid. Doses of 50,0 and 500,0 mg/kg MT have a polytropic effect on the body of male rats and are effective. DSD for humans at the level of 0.05 mg/kg is justified based on the inactive dose at the level of 5.0 mg per 1 kg of body weight, established in a 12-month chronic experiment conducted on male rats, and the reserve coefficient of 100 (taking into account the unexpressed specific and long-term effects).

Effect of neonatal administration of the opioid peptide dalargin on long-term cerebral consequences of antenatal hypoxia

2018 ◽  
pp. 31-36
Author(s):  
А.А. Симанкова ◽  
Е.Н. Сазонова ◽  
О.А. Лебедько
Keyword(s):  
Free Radical ◽  
Female Rats ◽  
Male Rats ◽  
Brain Morphology ◽  
Control Group ◽  
Albino Rats ◽  
Antenatal Hypoxia ◽  
Area Ca1 ◽  
Hippocampal Area

Цель исследования - анализ влияния d/m-агониста даларгина (Tyr - D-Ala - Gly - Phe - Leu - Arg) на морфофункциональные показатели головного мозга у половозрелых белых крыс Вистар, перенесших антенатальную гипоксию. Методика. Крысы-самки подвергались воздействию гипобарической гипоксии с 15-х по 19-е сут. гестации. Потомство было разделено на 2 группы: 1) животным группы «Антенатальная гипоксия» (n = 12) интраперитонеально вводили 0,1 мл физиологического раствора с 2-х по 6-е сут. жизни; 2) животным группы «Антенатальная гипоксия + даларгин» (n = 17) в те же сроки интраперитонеально вводили даларгин в дозировке 100 мкг/кг. Группа «Контроль» (n = 25) включала потомство крыс-самок, не подвергавшихся действию гипоксии в период гестации. В гистологических препаратах головного мозга 60-суточных крыс-самцов исследуемых групп определяли площадь ядер и ядрышек нейронов II и V слоев неокортекса и поля СА1 гиппокампа. Активность процессов свободнорадикального окисления в гомогенатах головного мозга определяли методом хемилюминисценции. Поведенческие реакции оценивали в тестах «Открытое поле» и «Приподнятый крестообразный лабиринт». Результаты. У животных группы «Антенатальная гипоксия» выявлено уменьшение массы тела и массы головного мозга; уменьшение числа ядрышек в нейронах II слоя неокортекса и гиппокампа, уменьшение площади ядер нейронов V слоя неокортекса и снижение площади ядрышек нейронов всех исследованных зон; повышение локомоторной активности; активация свободнорадикального окисления в гомогенатах мозга. Введение даларгина уменьшало морфофункциональные церебральные последствия антенатальной гипоксии. Заключение. Показан эффект даларгина для коррекции отдаленных церебральных последствий перенесенной антенатальной гипоксии в эксперименте. The aim of the study was to analyze the effect of d/m-agonist dalargin (Tyr-D-Ala-Gly-Phe-Leu-Arg) on brain morphology and function in mature albino rats exposed to antenatal hypoxia. Methods. Female rats were exposed to hypobaric hypoxia from gestation day 15 to day 19 day. The offspring was divided into 2 groups: 1) the first group, antenatal hypoxia (n = 12), where rats were injected with 0.1 ml of saline from 2 to 6 days of life, 2) the second group, antenatal hypoxia + dalargin (n = 17), where rats were injected with the peptide dalargin (100 mg/kg, i.p.) from 2 to 6 days of life. The control group (n = 25) included offspring of intact female rats. The size of neuronal nuclei and nucleoli in neocortical layers II and V and hippocampal area CA1 were measured on histological slides of the brain from 60-day old male rats. Intensity of free radical oxidation was determined by chemiluminescence in brain homogenates. Rat behavior was evaluated using the open field test and the elevated plus-maze test. Results. Antenatal hypoxia decreased body weight and weight of cerebral hemispheres in 60-day old male albino rats compared with the control. Antenatal hypoxia decreased the number of neuronal nucleoli in layer II of the neocortex and hippocampal area CA1, reduced neuronal nucleus size in layer V of the neocortex and the total area of neuronal nucleoli in all examined brain areas of 60-day-old male albino rats. Animals of this experimental group displayed increased motor activity. The chemiluminescence study of brain homogenates from 60-day-old animals showed increased free radical generation in brain tissues. Administration of dalargin reduced the morphofunctional cerebral consequences of antenatal hypoxia. Conclusion. Dalargin can be used for correcting long-term cerebral consequences of antenatal hypoxia.

scholarly journals Long-term and acute safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) in juvenile and adult dogs

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kari L. Riggs ◽  
Scott Wiseman
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Clinical Pathology ◽  
Control Group ◽  
Combination Drug ◽  
Milbemycin Oxime ◽  
Safety Studies ◽  
Chewable Tablets ◽  
Long Term Studies

Abstract Background The combination of milbemycin oxime (MO) and lotilaner (Credelio® Plus) is a novel systemic endectocide that provides month-long effectiveness in dogs after a single oral treatment. The safety of Credelio® Plus flavored chewable tablets was investigated in three target animal safety studies. Two studies (one in juveniles and one in adults) evaluated the long-term safety, and one study evaluated the acute safety of the product when administered orally at the upper end of the recommended dose range (0.75–1.53 mg/kg MO and 20–41 mg/kg lotilaner) and multiples of this dose. Methods The objectives of these studies were to determine the long-term and acute safety of MO and lotilaner flavored chewable tablets in healthy dogs. All three studies were randomized, blinded, parallel-group design studies in healthy Beagle dogs. In each of the two long-term studies, 32 dogs were randomized among four groups to untreated controls or to treated groups at target doses of 1X, 3X, or 5X. Treatment was administered on seven (adult dogs) or nine (juvenile dogs) occasions with dosing every 4 weeks. In the acute study, 48 dogs were randomized among four groups to untreated controls or to treated groups at 1X, 3X, or 6X. In all three studies, the control group was administered placebo tablets. All dogs were fed 30 to 45 min prior to treatment and the assessment of safety was based on health observations, complete physical/neurological examinations, and food consumption. For the long-term safety studies, safety assessments also included clinical pathology evaluations (hematology, clinical chemistry and urinalysis), body weight, pharmacokinetic blood collections, and macroscopic and microscopic examinations of collected tissues. Results MO and lotilaner did not induce any treatment-related adverse effects based on health observations, physical/neurological examinations, or food consumption in the long-term or acute studies. Additionally, in the long-term studies, MO and lotilaner did not induce any treatment-related effects on clinical pathology, body weight, and macroscopic and microscopic examinations. Conclusions These three studies demonstrate that Credelio® Plus has a wide safety margin when administered at monthly intervals to puppies and dogs at the high end of the commercial dose band. Graphic Abstract

scholarly journals Subacute Toxicity Profile of Lacidipine Nanoformulation in Wistar Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Rupesh Shirodkar ◽  
Chandrasekhar Misra ◽  
Chethan GH ◽  
Pallavi Shetty ◽  
Zenab Attari ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Testis Weight ◽  
Delayed Effect ◽  
Male And Female Rats

The present study was aimed at investigating the safety of Lacidipine (LCDP) loaded nanostructured lipid carriers (NLCs) in Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during 28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrificed on the 29th day. Study revealed no signs or symptoms of toxicity or morbidity. No significant changes in the body weight were observed between treated and control group. Significant increase in left testis weight and liver weight was observed in male and female rats, respectively. Haematological estimation revealed significant decrease in haemoglobin count in male rats while female rats showed significant increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological changes were observed. No delayed effect was noted in satellite group. The results indicate that developed LCDP loaded NLCs are safe when administered orally in rats.

Long-term Behaviour of 239Pu, 241Am and 233U in Different Bones of One-year-old Rats: Macrodistribution and Macrodosimetry

1984 ◽  
Vol 3 (6) ◽  
pp. 469-483 ◽  
Author(s):  
W. Sontag
Keyword(s):  
Body Weight ◽  
Relative Concentration ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Old Rats ◽  
One Year ◽  
The Individual ◽  
Suitable Reference

1 Female and male rats of the Sprague-Dawley strain, aged about 13 months, were injected intravenously with monomeric 239Pu-(30.7 kBq/kg), 241Am-(54.8 kBq/kg) or 233U-citrate (56.6 kBq/kg) and killed between 7 and 540 days after injection. 2 In both sexes the wet skeletal weight was proportional to body weight; however, the skeletal weight of female rats remained constant, whereas the skeletal weight, and body weight, of male rats increased as a function of age. 3 The initial skeletal deposition decreased in the order 239Pu > 241Am > 233U and for americium and uranium was greater in male rats. The 'half-time' of retention of plutonium and americium was considerably greater than 1 year but the corresponding values for uranium were 140 (females) and 80 (males) days. 4. The relative concentration of the radionuclides in the skeleton varied between 0.2 and 2.0, the variation was greatest for plutonium and lowest for americium and decreased with increasing time after injection. 5 For calculation of the nuclide content of the whole skeleton the most suitable reference bone was found to be the humerus in the case of uranium, and the femur and humerus for plutonium and americium. 6 The cumulative mean skeletal absorbed radiation dose 1 year after injection decreased in the order 239Pu > 241 Am > 233U; for plutonium it was equal for both sexes, whereas for americium and uranium it was 1.5 times higher in male than in females rats. In the individual bones the cumulative dose was greatest in the vertebral column, except the tail, and lowest in the paws.

Short-Term and Long-Term Effects of Bisphenol A (BPA) Exposure During Breastfeeding on the Biochemical and Endocrine Profiles in Rats

2018 ◽  
Vol 50 (06) ◽  
pp. 491-503 ◽  
Author(s):  
Ana Santos-Silva ◽  
Egberto de Moura ◽  
Cintia Pinheiro ◽  
Elaine Oliveira ◽  
Patricia Lisboa
Keyword(s):  
Bisphenol A ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Long Term Effects ◽  
Adult Rat ◽  
Endocrine Profiles ◽  
And Control

AbstractNeonates can be exposed to bisphenol A (BPA) through placenta and milk, and BPA is associated with disorders such as precocious puberty and obesity. We evaluated the effects of BPA exposure during breastfeeding on the biochemical and endocrine profiles in young and adult rat progeny. From postnatal day (PND) 3 to 15 dams were divided into low-dose BPA treatment [50 μg/kg/day s.c. (BPA-LD)], high-dose BPA treatment [5 mg/kg/day s.c. (BPA-HD)], and Control (vehicle) groups. Milk was collected at PND15 and 21, which represents the end of exposure and 6 days after withdrawal, respectively. Dams were euthanized at weaning. Offspring of both genders were euthanized at PND15, 21, and 180. Milk estradiol levels were lower in the BPA-HD group than in the control group at PND 15; however, they were higher at PND21. Female rats whose mothers were BPA-exposed showed more significant differences from those in the control group, including better glycemic control and lipid profiles and higher food intake without higher adiposity, in adulthood than in the weaning period, when they presented with higher adiposity and hyperestrogenism. Conversely, male rats showed more abnormalities after BPA exposure compared to control rats, including insulin, leptin, testosterone, and thyroid hormone changes, when young but exhibited fewer alterations in adulthood, with increase only in LDLc in the BPA-HD rats. Taken together, the present findings suggest that exposure to BPA exclusively through milk affects adiposity, metabolism, and/or hormones of offspring in the short and long term, possibly compromising normal development in both sexes.

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