Testicular Lesions in Rats Treated with a Sympatholytic Hypotensive Agent (Losulazine)

1989 ◽  
Vol 8 (3) ◽  
pp. 525-538 ◽  
Author(s):  
G. M. Mesfin ◽  
D. F. Morris ◽  
W. J. Seaman ◽  
T. A. Marks
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Body Weight Gain ◽  
Clinical Signs ◽  
Blood Chemistry ◽  
Vehicle Control ◽  
High Dose ◽  
Weight Changes ◽  
Tubular Atrophy ◽  
Testicular Lesions

Groups of 25 male Sprague-Dawley rats were treated orally with losulazine at 0 (vehicle control), 4, 8, 16, or 32 mg/kg/day for 1 year. Daily clinical signs, weekly food consumption and body weight changes, and terminal hematologic and blood chemistry values were evaluated. Terminal urinalysis in 10 randomly selected rats from all groups and levels of serum luetinizing hormone, prolactin, and testosterone from control, low-, and high-dose groups were also evaluated. Fertility was determined in eight randomly selected rats from each group at 35–49 weeks. Reversibility of breeding performance was evaluated in 10 rats treated for 30 weeks and allowed to recover for 17 weeks. Selected organs were weighed and the testes and epididymides were microscopically evaluated in all rats that survived through the 1 year treatment period. Rats treated with losulazine showed dosage-dependent ptosis, somnolence, fecal softening, and decreased food consumption with a corresponding retarded body weight gain. There were no biologically significant changes in hematologic, blood chemistry, or urinalysis values between treated and control rats. Relative spleen, heart, adrenal, and brain weights were increased in treated rats. There was a reversible dosage and time-dependent decreased fertility in rats treated with losulazine for 6–12 months. The incidence of testicular tubular atrophy/degeneration, usually confined to the subcapsular areas of the testes, and concentration of degenerate ge.minal cells in the epididymides, were increased in treated compared to vehicle control rats. Testicular lesions were not dosage related, were minimal to mild after 1 year of treatment, and were not attended by a decrease in relative testicular weights. Decreased fertility was not correlated with the apparently treatment-related testicular lesions. It could not be determined whether the minor testicular lesions seen in rats treated with losulazine were related to stressful conditions the rats were apparently under or to the effects of the drug on the hypothalamus-pituitary-gonadal axis or the sympathetic nervous system.

Tamarind Seed Polysaccharide

2013 ◽  
Vol 32 (3) ◽  
pp. 198-208 ◽  
Author(s):  
James T. Heimbach ◽  
Hiroshi Egawa ◽  
Palma Ann Marone ◽  
Mark R. Bauter ◽  
Elke Kennepohl
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Consumption ◽  
Body Weight Gain ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Female Rats ◽  
Feed Consumption ◽  
Test Substance ◽  
Tamarind Seed

Forty male and 40 female Crl:SD® CD® IGS rats were fed diets containing 0, 40 000, 80 000, or 120 000 ppm tamarind seed polysaccharide (equivalent to 3450.8, 6738.9, or 10 597.1 mg/kg bw/day and 3602.1, 7190.1, or 10 690.7 mg/kg bw/day for males and females, respectively) for 28 days. Animals were observed for adverse clinical signs, body weight, feed consumption, hematology and clinical chemistry parameters, urinalysis values were recorded, and at the end of the study the rats underwent a full necropsy. Functional Observational Battery (FOB) and Motor Activity (MA) tests were performed on all animals. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption and food efficiency, FOB or MA findings associated with the administration of tamarind seed polysaccharide. Initial statistically significant decreases in body weight gain and food consumption resolved after the first week and were considered the result of reduced palatability. There were no adverse changes in hematology, coagulation, clinical chemistry or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, estrus cycle, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study and based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for tamarind seed polysaccharide in the diet was the highest concentration tested of 120 000 ppm (equivalent to 10 597 mg/kg bw/day and 10 691 mg/kg bw/day for male and female rats, respectively).

Studies of the Toxicological Potential of Capsinoids: IV. Teratology Studies of CH-19 Sweet Extract in Rats and Rabbits

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 41-57 ◽  
Author(s):  
Bruce K. Bernard ◽  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Body Weight ◽  
Sex Ratio ◽  
Food Consumption ◽  
Clinical Signs ◽  
Pathological Finding ◽  
High Dose ◽  
Corpora Lutea ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level

In order to evaluate the safety of CH-19 Sweet extract that contains capsinoids, teratology studies were conducted in pregnant Sprague-Dawley rats (20 rats per group) and pregnant New Zealand white rabbits (17 to 22 animals per group). The test substance was administered to rats by gavage for 11 days on gestation days 7 to 17 at doses of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg and to rabbits for 13 days on gestation days 6 to 18 at doses of 0 (vehicle), 0.25, 0.5, and 1.0 ml/kg. As the concentration of capsinoids in CH-19 Sweet extract was 72.2 to 75.05 mg/ml, the resulting dose of capsinoids administered to rats was 90.25, 180.5, and 361 mg/kg, and to rabbits was 18.76, 37.53, and 75.05 mg/kg in the vehicle, low-, mid-, and high-dose groups, respectively. In the rat study, no deaths occurred in any group and there were no test substance–related changes or abnormalities in clinical signs, body weight, food consumption, or gross pathological findings. There were no test substance–related changes in the number of corpora lutea, number or index of implantations, index of embryofetal deaths, number of live fetuses, sex ratio, fetal body weight at the end of the gestation period, or abnormalities in the placenta of live fetuses. There were no test substance–related abnormalities or variations in the external, skeletal, or visceral examinations of live fetuses. It was concluded that the test article caused neither teratogenic effects nor abnormalities in the progression of ossification. In the rabbit study, there were no test substance–related effects on clinical signs, body weight, food consumption, or necropsy findings. There were neither test substance–related abortions nor test substance–related effects on the number of corpora lutea, or number or index of implantations. There were no test substance–related effects on the number of dead embryos/fetuses, the number of live fetuses, sex ratio, body weight of live fetuses, or gross pathological finding in the placentas. There were no test substance–related external abnormalities or incidences of visceral or skeletal abnormalities or variations, and there were no test substance–related effects on the progress of ossification in any group. The authors concluded the no observed adverse effect level (NOAEL) of CH-19 Sweet extract containing capsinoids on pregnant animals and fetal development/growth was >5.0 ml/kg/day (>361 mg/kg/day as capsinoids) in rats and >1.0 ml/kg/day (>75.05 mg/kg/day as capsinoids) in rabbits.

scholarly journals A 90-Day Oral Toxicity Study of an Ethanolic Root Extract of Caesalpinia bonduc (L.) Roxb. in Wistar Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Mariette Sindete ◽  
Adam Gbankoto ◽  
Razack Osseni ◽  
Nounagnon Darius Tossavi ◽  
Simon Azonbakin ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Body Weight Gain ◽  
Clinical Signs ◽  
Relative Weight ◽  
Drug Effects ◽  
Root Extract ◽  
Weight Changes ◽  
Oral Toxicity ◽  
Urinary Parameters

Background. Plant medicine is the oldest form of health care known to mankind; hence, studies on their safety for use are essential for the control of adverse drug effects. In Benin, Caesalpinia bonduc is one of many medicinal plants used as aphrodisiac, and for treatment of various ailments including prostatic hyperplasia. Despite its numerous ethnomedicinal benefits, toxicological information associated with its chronic use is currently limited. Objective. The present study therefore assessed the toxicity of an ethanolic root extract of Caesalpinia bonduc in Wistar rats. Methods. Caesalpinia bonduc root extract was administered by oral gavage at doses of 31.25, 125, and 500 mg/kg/day for 90 days to male Wistar rats, after which body weight changes, food consumption, urinary parameters, hematological and blood biochemical parameters, organ weights changes, gross pathology, and histopathology of vital organs were assessed. Results. There were no death or abnormal clinical signs, no significant changes in body weight gain or urinary parameters, and no changes in necropsy and histopathology findings of vital organs associated with extract treatment. However, some indices such as erythrocytes, total cholesterol, and aspartate amino transferase increased in rats treated with high doses of the extract, as well as relative weight of testes, followed by a decrease in food intake and prostate relative weight. Conclusion. The results indicate that an ethanolic root extract of Caesalpinia bonduc does not cause significant adverse effects and suggest its tolerability up to 500 mg/kg for daily administration of 90 days.

scholarly journals Safety assessment of the standardized aqueous extract from solid-state cultured Xylaria nigripes (Wuling Shen) in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ming-Nan Lai ◽  
Hui-Chen Hsu ◽  
Lean-Teik Ng
Keyword(s):  
Body Weight ◽  
Solid State ◽  
Aqueous Extract ◽  
Structural Changes ◽  
Histopathological Examination ◽  
Body Weight Gain ◽  
Control Group ◽  
High Dose ◽  
Weight Changes ◽  
Hematological Analysis

Abstract Background Xylaria nigripes (Koltz.) Cooke, also known as Wuling Shen, is a high-value medicinal mushroom. It is a herbal medicine traditionally used for treating insomnia, trauma and depression. However, its toxicity has never been systematically evaluated. This study aimed to evaluate the safety of a standardized aqueous extract (XNE), an ingredient of commercial products, prepared from solid-state cultured X. nigripes in rats. Methods A 90-day subchronic toxicity study was conducted by oral administration of XNE at daily doses of 20, 1000 and 2000 mg/kg body weight to Sprague-Dawley rats of both sexes, and the control group was given distilled water (vehicle). All animals were checked daily for general behavior, body weight changes and signs of toxicity. At the end of the treatment period, hematological analysis, biochemical analysis and histopathological examination of organs were conducted. Results At tested concentrations, oral XNE administration caused no treatment-induced adverse effects on general health, body weight gain, relative organ weights, and hematological and biochemical parameters. Histopathological results also showed no significant structural changes in organs even in high-dose XNE-treated animals. Conclusion This study suggests that treatment with XNE for 90 days does not produce significant toxicity, even up to 100 fold (2000 mg/kg body weight/day) of the recommended daily intakes. Therefore, the use of XNE as herbal medicines is considered to be relatively safe.

scholarly journals Lack of Neuropathological Changes in Rats Administered Tedizolid Phosphate for Nine Months

2014 ◽  
Vol 59 (1) ◽  
pp. 475-481 ◽  
Author(s):  
Michael J. Schlosser ◽  
Hiromi Hosako ◽  
Ann Radovsky ◽  
Mark T. Butt ◽  
Dragomir Draganov ◽  
...  
Keyword(s):  
Body Weight ◽  
Optic Nerve ◽  
Body Weight Gain ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Once Daily ◽  
Clinical Observations ◽  
Activity Measures ◽  
Dose Levels ◽  
Neurobehavioral Effects

ABSTRACTTedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (−6.7%) and females (−5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.

Effect of continuous infusions of CCK-8 on food intake and body and pancreatic weights in rats

1988 ◽  
Vol 254 (1) ◽  
pp. R17-R22 ◽  
Author(s):  
L. Lukaszewski ◽  
M. Praissman
Keyword(s):  
Food Intake ◽  
Food Consumption ◽  
High Dose ◽  
Weight Changes ◽  
Body Weight Changes ◽  
Jugular Veins ◽  
Indirect Measure ◽  
Pancreatic Growth ◽  
Infusion Period

The ability of cholecystokinin (CCK) to act as a long-term satiety factor was assessed by its continuous infusion into the jugular veins of rats. Animals receiving a low dose of cholecystokinin octapeptide (CCK-8) (0.6 microgram CCK-8.kg body wt-1.h-1) did not show any significant differences in body weight changes or in food consumption from rats receiving saline and a group of unoperated controls over the 7-day infusion period. A 19.3-fold greater dose of CCK-8 (11.6 micrograms.kg body wt-1.h-1) did cause a significant decline in food consumption for the first 4 days compared with saline-infused rats (P less than 0.05) and unoperated controls (P less than 0.01). Rats receiving a high dose of CCK gained weight at a slower rate than rats receiving saline, but this effect lasted only 2 days and was not significant. Pancreatic growth was used as an indirect measure of elevated CCK levels in these animals. The infusion of 0.6 microgram CCK-8.kg body wt-1.h-1 did not lead to sufficiently elevated peptide levels to promote pancreatic growth. In contrast, those rats receiving a high dose of CCK-8 had significantly greater pancreatic weights (P less than 0.01) compared with saline-treated rats and unoperated controls. These results indicate that CCK-8, when administered continuously and in a large enough dose, can suppress food intake in rats for a period of several days before losing its effectiveness.

scholarly journals Thirteen-Week Oral Toxicity Study of HVC1 in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Kyungjin Lee ◽  
Ho-Young Choi
Keyword(s):  
Hematological Parameters ◽  
Clinical Signs ◽  
Ethanol Extract ◽  
New Drugs ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Weight Changes ◽  
Oral Toxicity ◽  
Blood Biochemical

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.

Nutritional and metabolic adaptations to prolonged sleep deprivation in the rat

1993 ◽  
Vol 264 (2) ◽  
pp. R376-R387 ◽  
Author(s):  
C. A. Everson ◽  
T. A. Wehr
Keyword(s):  
Body Weight ◽  
Sleep Deprivation ◽  
Food Consumption ◽  
Time Course ◽  
Body Weight Gain ◽  
Clinical Chemistry ◽  
Plasma Cholesterol ◽  
Skin Lesions ◽  
Weight Regulation ◽  
Body Weight Regulation

To understand how and why sleep deprivation is physically harmful, we explored the possible causal relationship between its two main effects, 1) negative energy balance and 2) a composite of symptoms that resemble protein malnutrition, both of which occur despite increased food consumption. We provided balanced diets augmented with either protein or calories (by increased fat content) to freely moving rats. Interactions between sleep deprivation symptoms and energy and protein supplies were assessed from measurements of body weight regulation, consumption of macronutrients, clinical chemistry and hematology profiles, and physical appearance. The results indicate that sleep deprivation causes malnutrition, which is secondary to increased energy expenditure. Even though food consumption remained normal in sleep-deprived rats fed a diet of high protein-to-calorie ratio, body weight loss was more than 16% of baseline, development of skin lesions was hastened, and longevity was shortened by 40% compared with sleep-deprived rats fed the calorie-augmented diet. Food consumption of the calorie-fed rats was lower during baseline than that of the protein-fed group but during sleep deprivation increased to amounts 250% of normal without net body weight gain. Despite a fat-laden diet the calorie-fed hyperphagic group did not have abnormal levels of plasma cholesterol, triglycerides, or glucose, indicating accelerated turnover of nutrients. As would be consistent with calorie malnutrition, pronounced clinical chemistry or hematological abnormalities were not found in any group. Beneficial effects of the calorie-augmented diet are attributed to 1) caloric density of fat, 2) induction of hyperphagia, and 3) efficiency of utilization of fat. We conclude that diet composition interacts strongly with sleep deprivation, affecting the time course and development of pathologies, whereas it exerted negligible influence on body weight regulation under normal conditions.

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