A Teratological Evaluation and Postnatal Behavioral Screen of KF-868 In Rats

1985 ◽  
Vol 4 (1) ◽  
pp. 91-110 ◽  
Author(s):  
A. M. Hoberman ◽  
W. M. Weatherholtz ◽  
R. S. Durloo

The effects of a new experimental drug, KF-868, were investigated after administration to pregnant Sprague-Dawley rats at 0(vehicle), 0.1, 2.0, and 40.0 mg/kg per day during Days 7 through 17 of gestation by examination of term fetuses and naturally delivered offspring. Pregnant rats administered 0.1, 2.0, and 40.0 mg/kg per day gained significantly more weight during the dosage period than did the vehicle control group. Treatment-related physical signs, bloody crust on nose and stains on fur, were observed in the high dosage group. Fetal viability was significantly increased, and resorptions were significantly decreased for the mid and high dosage groups, when compared with the control group. Average fetal body weights for cesarean-delivered fetuses were less for the 40.0 mg/kg per day dosage groups than for the vehicle control group. Visceral and skeletal evaluations of fetuses revealed no difference between the control and test groups. Percent survival of pups was significantly less for the high dosage group than for the control group. Average rat body weights prior to mating for the high dosage group were generally less than for the control group. All physical and functional developmental values were comparable among the control and test groups. Evaluation of postweaning parameters of pups revealed no significant difference in sex maturation, behavior (open-field and water maze), and reproductive capacity. Average body weight gains during the 9-week growth period before mating were significantly less for the 40.0 mg/kg per day dosage group F1 generation female rats. Toxicity in fetuses and offspring was observed only at the highest dosage level. Dosage-dependent, significant increases in maternal body weight gain, as compared with control values, occurred for doses in the 3 KF-868-administered groups. These results indicate that 0.1 and 2.0 mg/kg per day dosages of KF-868 were not lethal and did not produce any adverse effects on the morphological or functional development of offspring. Toxicity was evident in offspring and fetuses of dams administered 40.0 mg/kg per day KF-868, 40,000 times as high as the daily therapeutic dose.

2016 ◽  
Vol 78 (5-5) ◽  
Author(s):  
Norazlanshah Hazali ◽  
Nurul Nadia Mohd Nazri ◽  
Muhammad Ibrahim ◽  
Mashita Masri

Acalypha indica is one of the medicinal plants that have been used since ages to treat various diseases such as pneumoniae, asthma and skin diseases. This study aimed to explore the subchronic toxicity effect of Acalypha indica on Sprague Dawley rats based on haematological and biochemical parameters. The extract of Acalypha indica was prepared by aqueous extraction technique. 48 Sprague Dawley rats aged 7 weeks, weighing 150-200g were randomly divided into four groups, 6 animals per gender. A control group received water vehicle while three treated groups received the extract at dosage of 100 (low dosage group), 200 (medium dosage group) and 300 (high dosage group) mg/kg body weight. The sample was administered orally by using oral gavage daily for 90 days. No sign of toxicity and mortality was recorded in all groups throughout the study. There were no significant different (p>0.05) in body weight gain, food and water intake between control and treatment group. However, there was significant different in uric acid between control and high dosage group of male and female rats but the mean were in normal range. There were also reduced in mean of urea and creatinine in all dosage group of male and urea for all dosage group of female. Statistically significant reduced in urea was recorded between control and high dosage group of male only. Other parameters showed no significant different between control and treatment groups. Therefore, Acalypha indica is safe for human consumption and might be potential in reducing kidney damage problem.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Sachin Jain ◽  
Gajendra Pratap Choudhary ◽  
Dinesh Kumar Jain

Objectives. Pharmacological and antifertility activity evaluation ofJatropha gossypifoliain rats.Methods. The antifertility activity of the extracts ofJatropha gossypifoliain rats was evaluated using two experimental animal models. Estrogenic activity was evaluated in immature female rats using ethinyl estradiol as standard. Anti-implantation and early abortifacient activity was performed in female Wistar rats by determining the number of implantations and implantation resorptions.Results. In estrogenic activity evaluations, the ethanolic and aqueous extracts offered significant estrogen-like activity at 400 mg kg−1p.o. by increasing the uterine weight compared to vehicle control group. Ethanolic extract (400 mg kg−1, p.o.) treatment significantly decreased the number of implants and increased the number of resorptions compared to vehicle control group.Conclusion. The results of the present study provide the evidence of the anti-fertility activity ofJatropha gossypifoliaas claimed in the traditional use. The results are consistent with the literature reports related to the antifertility effect of flower extracts ofJatropha gossypifolia.


2017 ◽  
Vol 15 (1) ◽  
pp. 40-43
Author(s):  
Anup Pandeya ◽  
Chandra Bhushan Jha ◽  
Smriti Karki ◽  
Gajendra Prashad Rauniar

Background and Objectives: Nephrotoxicity is one of the limiting factors for using doxorubicin as an anticancer chemotherapeutic. Reactive oxygen species and cytokines have been implicated in the nephrotoxicity induced by doxorubicin. The main objective of the present study is to identify and compare the histomorphological features in kidneys of albino rats and gross morphological features such as weight of rats and weight of the kidneys due to administration of doxorubicin. Materials and Methods: In the study, albino rats were taken as the animal model. Sixty animals were taken as the sample size. They were divided into two equal groups: experimental (n=30) and control (n=30). Rats of experimental group were treated with anticancer drug doxorubicin at a single intraperitoneal dose of 10 mg/kg body weight while the Control group of rats received a similar volume of 0.9% normal saline. The ethical clearance was taken prior to the research from IERB committee BPKIHS Dharan.  Results: Our results showed that there was high effect of drug in experimental groups of rats. It was seen that there was significant decrease in the body weight and weight of kidneys. The final body weight and kidney weight between experimental and control group showed the significant difference. Similarly there were no significant differences in the normal architecture between the male and female rats. The normal renal histological features were seen on the kidneys in the control group whereas the rats intervened with the drug had some disrupted histological features which reveal the toxicity of the drugs in the kidneys. Conclusion: The study showed toxicity of the drug in the kidneys of experimental groups of rats irrespective of gender and suggest that doxorubicin causes significant loss of the body weight and weight of kidneys and causes the disruption in the normal histological features.


2013 ◽  
Vol 32 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Valerie T. Politano ◽  
Danielle McGinty ◽  
Elise M. Lewis ◽  
Alan M. Hoberman ◽  
Mildred S. Christian ◽  
...  

The estrogenic potential of lavender oil was evaluated in a percutaneous uterotrophic bioassay in immature female rats. Four groups of 10 immature female rats each were randomly selected on postpartum day (PPD) 16. During the 3-day treatment period (PPDs 19-21), the immature rats were separated from the dams, caged in groups of 5 in a litter box for 6 hours, and administered the vehicle control article (corn oil) or lavender oil at 20 or 100 mg/kg per day. All dosages were administered as a 5 mL/kg volume in a Hilltop Chamber (25 mm diameter; absorbent material removed) placed on the shaved back of each immature rat, and secured with micropore tape and Vetrap. A positive control group was gavaged twice daily with 2.5 μg/kg per day of 17α-ethinyl estradiol. Daily observations included viability, clinical signs, body weights, and body weight gains. All rats were euthanized 24 hours after the third and final treatment, the uteri and ovaries were removed, and the paired ovaries and wet and blotted uterine weights were recorded. No unscheduled deaths occurred. No skin reactions were observed. Both dosages of lavender oil significantly reduced body weight gains after the third day of treatment, but terminal body weights and mean absolute and relative uterine weights did not differ significantly from vehicle control values. Positive controls showed significant increases in body weight and increased mean absolute and relative uterine weights as expected. Based on these data, lavender oil, at dosages of 20 or 100 mg/kg, was not active in the rat uterotrophic assay and gave no evidence of estrogenic activity.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Rungsima Wanitphakdeedecha ◽  
Sasima Eimpunth ◽  
Woraphong Manuskiatti

Background. Mucopolysaccharide polysulphate (MPS) has been used in medicine as an anti-inflammatory and antithrombotic agent for over 50 years. Its chemical structure permits considerable hydrogen bonding with adjacent water molecules, which effectively leads to hydration of the surrounding tissue. In addition, it stimulates endogenous hyaluronate synthesis, resulting in an increase in water-binding capacity and viscoelasticity of the skin.Objective. To study the efficacy of 0.1% MPS on hydration and elasticity of human skin.Methods. The first part of this study was a randomized double blind placebo-controlled study which included 60 female volunteers aged 30–45 years with dry skin, defined by Corneometer CM 825. The volunteers were treated with either 0.1% MPS or vehicle control. All subjects were asked to apply 1 g of cream to their face twice daily for a total period of 4 weeks. Skin hydration and elasticity were measured at baseline and week 4 with Corneometer CM 825 and cutometer MPA 580, respectively, at forehead and both cheeks. The second part of this study focused on the efficacy of 0.1% MPS on skin hydration after single application. 20 female volunteers aged 30–45 years with dry skin, defined by Corneometer CM 825, were recruited to the study. All subjects were asked to apply 2 g of 0.1% MPS cream on entirely randomly selected forearm. Skin hydration at the middle of both forearms was measured at baseline, immediately after application, and every 1 hour after application for a period of 10 hours.Results. 57 subjects (28 in vehicle control group, 29 in MPS) completed treatment protocol. The baseline skin hydration of both groups was not significantly different (P=0.47). Hower, there was a statistically significant difference in skin hydration at 4 weeks between MPS and placebo group (P=0.01). Skin elasticity was significantly improved at week 4 in both groups (vehicle-control,P<0.01, and MPS,P<0.01). However, no significant difference in skin elasticity between MPS and vehicle-control group was noted (P=0.15). Lastly, there was a statistically significant improvement in skin hydration after a single application (P<0.01). This improvement was maintained for 10 hours.Conclusions. MPS provided improvement of skin hydration but not skin elasticity in woman with dry skin, compared with vehicle control. And MPS improved the skin hydration for at least 10 hours after single application.


Author(s):  
Buddhadeb Ghosh ◽  
Suman Yadav ◽  
Ravi Kant Sharma

Introduction: Aluminium (AL) exposure leads to neurotoxicity and many problems in the body. AL role in Alzheimer's Disease (AD) is unknown and controversial to the scientists. According to World Health Organisation (WHO) provisional tolerable weekly intake of AL is 2 mg/kg body weight. Moderate intake of alcohol may favour body in coronary heart disease and diabetes mellitus, etc. Aluminium being cheaper along with increased consumption of alcohol, mixed with each other may induce neurotoxicity. Aim: The study was designed to identify the effects of AL in cerebrum of rats in presence of ethanol co-exposure. Materials and Methods: An experimental study was carried out at Dr. RP Government Medical College, Kangra and Government Medical College, Amritsar, India after due approval from the Institute Animal Ethics Committee. Thirty-two wistar rats were divided into one vehicle control and three experimental groups. Group I received the normal saline water as vehicle control group. Group II received AL chloride 4.2 mg/kg body weight as experimental group. Group III received ethanol 1 gm/kg body weight as experimental group. Group IV received both AL chloride 4.2 mg/kg body weight and ethanol 1 gm/kg body weight as experimental group. After treatment, brain cortex was processed for histopathological observation under microscope. Results: Cerebral cortex showed normal architecture of the brain with haematoxylin and eosin staining and cresyl violet staining and modified Bielchowsky silver staining in low and high magnification in vehicle control group. Experimental group treated with AL and ethanol separately showed reduction in the count of pyramidal cells with moderate neuronal degeneration with pyknotic nuclei. Vacuolar changes and pericellular spaces around the necrotic neurons were also seen. Combined AL and ethanol treated group showed acute neurodegeneration and necrosis of cortex indicating chromatolysis and loss of substances and Neurofibrillary Tangle (NFT) and plaque. Conclusion: It has been concluded that the ethanol induced the effects of AL on the cerebrum and plays a significant role in AD pathogenesis.


Author(s):  
U. I. Tesarivska ◽  
G. І. Kocjumbas

The article presents the results of studies on the effects of citric acid on the female’s body. The studies were performed on white laboratory rats of the Wistar line, which at the age of 3 - 3.5 months with a body weight of 192 - 210 g were divided into two groups of 4 individuals in each. The animals of the experimental group were fed by citric acid at a concentration of 80 mg/l of drinking water during the period physiological and puberty, fertilization and pregnancy. A control group of female rats was fed by water. The animals had free access to drinkers and food. Indicators of embryogenesis, leukocyte profile of blood and body weight of animals, weighting factor, histological changes of the liver were determined. Female rats were found to have no abortions or premature births, however, the number of corpora lutea of pregnancy decreased by 19.2%, although there was no significant difference in control. The number of implantation sites per female was significantly lower by 28.8%. The mortality rate of embryos was 15.8%, which is 3.8 times higher than in intact animals. Regarding white blood cells, the analysis of the results indicates a tendency to increase the percentage of eosinophils in 2 times in the relation to the animals in the control group on the background of a probable increase in leukocytes by 42.4%. The applied dose of citric acid caused certain changes in the macro- and microstructure of the liver. It is macroscopically established that under the influence of citric acid the organ is slightly enlarged, sluggish consistency and changed its color from light red to light brown. The relative weighting factors of the liver are probably higher in the relation to the control (52.12 ± 8.16 g/kg vs 43.38 ± 1.96 g/ kg). The results of morphological studies indicate a partial violation of the lamellar structure of the organ in the centro-lobular region, which is due to turbid swelling of the cytoplasm of hepatocytes. In most cells, the contours are blurred, the cytoplasm is poorly stained, their nuclei are weakly basophilic, and hepatocytes with a lysed nucleus in a necrobiosis condition also occur. However, among dystrophic altered cells are clearly isolated hepatocytes with a uniformly colored basophilic cytoplasm, nucleus, rich in chromatin, which indicated the activation of reparative processes. Kupffer cells in this area are mostly round, located in the lumen of the sinusoid. Therefore, occurs a violation of lipoprotein complexes of cells and increase the permeability of cell membranes, which is reflected in the development of protein dystrophy with varying degrees of severity. Activation of reparative processes of hepatocytes is also determined.


2014 ◽  
Vol 84 (1-2) ◽  
pp. 5-11 ◽  
Author(s):  
Eun Y. Jung ◽  
Sung C. Jun ◽  
Un J. Chang ◽  
Hyung J. Suh

Previously, we have found that the addition of L-ascorbic acid to chitosan enhanced the reduction in body weight gain in guinea pigs fed a high-fat diet. We hypothesized that the addition of L-ascorbic acid to chitosan would accelerate the reduction of body weight in humans, similar to the animal model. Overweight subjects administered chitosan with or without L-ascorbic acid for 8 weeks, were assigned to three groups: Control group (N = 26, placebo, vehicle only), Chito group (N = 27, 3 g/day chitosan), and Chito-vita group (N = 27, 3 g/day chitosan plus 2 g/day L-ascorbic acid). The body weights and body mass index (BMI) of the Chito and Chito-vita groups decreased significantly (p < 0.05) compared to the Control group. The BMI of the Chito-vita group decreased significantly compared to the Chito group (Chito: -1.0 kg/m2 vs. Chito-vita: -1.6 kg/m2, p < 0.05). The results showed that the chitosan enhanced reduction of body weight and BMI was accentuated by the addition of L-ascorbic acid. The fat mass, percentage body fat, body circumference, and skinfold thickness in the Chito and Chito-vita groups decreased more than the Control group; however, these parameters were not significantly different between the three groups. Chitosan combined with L-ascorbic acid may be useful for controlling body weight.


1996 ◽  
Vol 271 (1) ◽  
pp. R48-R54 ◽  
Author(s):  
K. Ackroff ◽  
A. Sclafani

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.


2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.


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