Thirteen-Week Oral Toxicity Study of l-Glutamine in Rats

2004 ◽  
Vol 23 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Kazunori Mawatari ◽  
Miro Smriga ◽  
Takeshi Kimura
Keyword(s):  
Ketone Bodies ◽  
Recovery Period ◽  
Control Group ◽  
Standard Diet ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Urine Ph ◽  
Toxicological Effects ◽  
Adverse Effect Level ◽  
Hematology Parameters

l-Glutamine (Gln) is a semiessential amino acid used in enteral feeding in critically ill patients, and is contained in numerous dietary supplements available to the general public. This study evaluated toxicological effects of Gln in male and female Sprague-Dawley rats. Gln produced by Ajinomoto Co. (Tokyo, Japan) was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w), respectivelly. A control group of rats received only a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. Throughout the administration and recovery periods, no deaths were observed, and no changes in diet consumption, ophthalmologic findings, gross pathology, and histopathology were detected. Several changes in urine parameters (total protein, urine pH, and a positive incidence (±) of ketone bodies) were observed in the 2.5% and 5.0% groups at the end of the administration period. Minor increases were found in hematology parameters for the 5.0% group (platelet count, γ-globulin, lactate dehydrogenase [LDH]), but all changes were within physiological range. No effects of administration were observed in the 1.25% group. The no-observed-adverse-effect level (NOAEL) for Gln was estimated at 1.25% for both genders (males 0.83 ± 0.01 g/kg/day; females, 0.96 ± 0.06 g/kg/day).

Thirteen-Week Oral Toxicity Study of Branched-Chain Amino Acids in Rats

2004 ◽  
Vol 23 (2) ◽  
pp. 119-126 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Toyohisa Katsumata ◽  
Nobuo Nishimura ◽  
Kazunori Mawatari ◽  
...  
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Ketone Bodies ◽  
Body Weight Gain ◽  
Recovery Period ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Standard Diet ◽  
Oral Toxicity ◽  
Branched Chain

Branched-chain amino acids (l-isoleucine, l-valine, and l-leucine) are being increasingly used in sport supplements. This study evaluated toxicological and behavioral effects of l-isoleucine (Ile), l-valine (Val), and l-leucine (Leu) during a dosing study with male and female Sprague-Dawley rats. The amino acids were incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w). A control group of rats received a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine stability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. No significant, dose-related effects on body weight were found in rats fed a Leu-and Ile-supplemented diet. Val mixed into a diet at 5.0% ( w/ w) decreased slightly, but significantly body weight gain in females, but not males. Ile (5.0% w/ w) affected the urine electrolytes, protein, ketone bodies, urine glucose, and urobilinogen in both genders, yet the observed changes remained mostly within the range observed in controls. The random findings in hepatology and ophthalmology at the 13-week sacrifice were not considered toxicologically relevant to effects of the tested amino acids. No significant changes in organ weights were recorded. We estimate the no-observed-adverse-effect level (NOAEL) for Ile at 2.5% for both genders (male, 1.565 ± 0.060 g/kg/day; females, 1.646 ± 0.095 g/kg/day), Val at 5.0% for males (3.225 ± 0.135 g/kg/day) and 2.5% for females (1.853 ± 0.060 g/kg/day), and Leu at 5.0% for both genders (males, 3.333 ± 0.101 g/kg/day: females, 3.835 ± 0.257 g/kg/day).

scholarly journals A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats

2021 ◽  
Vol 58 ◽  
pp. 004695802110560
Author(s):  
Min Hong ◽  
Min Lu ◽  
Yimin Qian ◽  
Liping Wei ◽  
Yaqun Zhang ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Recovery Period ◽  
Safety Evaluation ◽  
Toxicity Assessment ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Renal Tubular Cells ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Renal Tubular

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

Thirteen-Week Oral Toxicity Study of L-Lysine Hydrochloride in Rats

2004 ◽  
Vol 23 (2) ◽  
pp. 113-118 ◽  
Author(s):  
Shoji Tsubuku ◽  
Masahiro Mochizuki ◽  
Kazunori Mawatari ◽  
Miro Smriga ◽  
Takeshi Kimura
Keyword(s):  
Amino Acid ◽  
Group Treatment ◽  
Recovery Period ◽  
Clinical Signs ◽  
Female Rats ◽  
Control Group ◽  
Standard Diet ◽  
Oral Toxicity ◽  
Male And Female ◽  
Male And Female Rats

l-Lysine hydrochloride (Lys) is an essential amino acid in humans and animals, and it is used in animal feeds, in prevention of herpes simplex recurrence, and cereal fortification in some developing countries. This study evaluated toxicological and behavioral effects of Lys during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/ w). A control group of rats received a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine stability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. In male and female rats in each concentration group, treatment-related changes were not observed in the clinical signs, body weights, diet consumption, water intake, ophthalmology, gross pathology, organ weights, or histology. A Lys-related drop in serum concentration and an increase in urine excretion of chlorides was a compensatory reaction to the ingested hydrochloride. No functional, biochemical, or histological changes in renal function were found. The no-observed-adverse-effect level (NOAEL) for Lys was estimated at 5.0% for both genders (male, 3.36 ± 0.12 g/kg/day; female, 3.99 ± 0.28 g/kg/day).

Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose studies

2009 ◽  
Vol 28 (10) ◽  
pp. 619-630 ◽  
Author(s):  
T. Kobayashi ◽  
N. Yasutake ◽  
K. Uchida ◽  
W. Ohyama ◽  
K. Kaneko ◽  
...  
Keyword(s):  
Oral Dose ◽  
Kluyveromyces Lactis ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Metabolic Activation ◽  
Blood Chemistry ◽  
Control Group ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Effect Level

A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by a two-step enzymatic process involving Sporobolomyces singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal aberration tests, with or without metabolic activation, were performed. These tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and no chromosomal aberrations in cultured fibroblast cells from Chinese hamster lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse peripheral blood following oral administration of GOS. In a 90-day repeated oral dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg to male and female Sprague-Dawley rats. There were no GOS-related changes in clinical signs, body weight, water intake, feed intake, urinalysis, ophthalmology, haematology, blood chemistry, organ weights, gross pathology or histopathology in any of the treatment groups compared to the control group. The no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in both males and females.

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.

scholarly journals Antioxidant and Hepatoprotective Activity of a New Tablets Formulation fromTamarindus indicaL.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jesús Rafael Rodriguez Amado ◽  
Ariadna Lafourcade Prada ◽  
Julio Cesar Escalona Arranz ◽  
Renato Pérez Rosés ◽  
Humberto Morris Quevedo ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Negative Control ◽  
Diet Group ◽  
Control Group ◽  
Standard Diet ◽  
Tamarindus Indica ◽  
Sprague Dawley ◽  
Group I

Hepatotoxic chemicals damage liver cells primarily by producing reactive oxygen species. The decoction of the leaves ofTamarindus indicaL. is used for liver disorders. In this work we evaluated the hepatoprotective activity of a tablet formulation of this plant. Thirty-five Sprague Dawley rats were randomly divided into five groups (n=7). First group (I) is control group, fed with standard diet. Groups II to V (hepatotoxic groups) were subjected to a subcutaneous injection of CCl4(0.5 mL/kg). Group II was negative control, fed with standard diet; group III was subjected to administration of Silymarin 150 mg/kg and groups IV and V were treated with tablets in dose of 100 mg/kg and 200 mg/kg, respectively. Lipid peroxidation and the activity of superoxide dismutase, catalase, and reduced glutathione were evaluated. Serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamine transferase, alkaline phosphatase, and a lipid profile were evaluated too. The tablets inhibit lipid peroxidation. The redox balance (SOD-CAT-GSH) remains normal in the experimental groups treated with tablets. The liver function using dose of 200 mg/kg of tablets was better than the other experimental groups. These results justify, scientifically, the ethnobotanical use of the leaves ofTamarindus indicaL.

scholarly journals Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan
Keyword(s):  
Body Weight ◽  
Toxicity Study ◽  
Morphological Alteration ◽  
Control Group ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Methanolic Extracts ◽  
Sprague Dawley Rats ◽  
Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

scholarly journals Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sittichai Koontongkaew ◽  
Orapan Poachanukoon ◽  
Seewaboon Sireeratawong ◽  
Thaweephol Dechatiwongse Na Ayudhya ◽  
Parirat Khonsung ◽  
...  
Keyword(s):  
Body Weight ◽  
Clinical Chemistry ◽  
Hematological Parameters ◽  
Safety Evaluation ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Zingiber Cassumunar

Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P<0.05). The weights of lung and kidney of treated females were increased (P<0.05). Treated males were increased in spleen and epididymis weights (P<0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.

scholarly journals Echography analysis altered in musculoskeletal, heart and liver associated with endothelial dysfunction of obese rat

2020 ◽  
Author(s):  
Alejandra Martínez Coria ◽  
Norma Angélica Estrada-Cruz ◽  
María Inés Pérez Ordoñez ◽  
Daniel H. Montes-Cortes ◽  
Leticia Manuel-Apolinar
Keyword(s):  
Body Weight ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Musculoskeletal System ◽  
Lower Extremities ◽  
Abdominal Ultrasound ◽  
Control Group ◽  
Standard Diet ◽  
Sprague Dawley ◽  
Distal Joint

Abstract Background: Modern imaging plays a central role in the care of obese patients, with an integral focus on its use and accessibility in individuals into this condition with alterations of various organs. Objective. To perform an echographical analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle in obese rats. Methods. Sprague Dawley rats (250±5 g) were used and divided in two groups: control group (C) fed with a standard diet, and the obese group (Ob) fed with a hyper caloric diet of high fructose-fat for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities.Results. Body weight in the Ob group was increased compared to the control group, (p <0.001); in addition, increased glucose, cholesterol and triglycerides were found in the Ob group vs the C group, (p<0.05), and as well as increased adhesion molecules ICAM-1 and, VCAM-1 (p<0.01). On ultrasound, 75% of the Ob group presented, showed 75% fatty liver and distal joint abnormalities. Conclusion. Endothelial dysfunction and changes at the level of the musculoskeletal system with the presence of joint cysts in the posterior region of the distal joint of the lower extremities and fat liver were observed in obese rodents.

scholarly journals The Effect of Tempeh Gembus Variations to Serum Levels of High Sensitivity C-Reactive Protein (hsCRP) and Serum Levels of Fibrinogen of Sprague Dawley Rats with Aterogenic Diet

2018 ◽  
Vol 25 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Partika Kharunia Dewi ◽  
Diana Nur Afifah ◽  
Ninik Rustanti ◽  
Mohammad Sulchan ◽  
Gemala Anjani
Keyword(s):  
Serum Levels ◽  
Negative Control Group ◽  
Positive Control ◽  
Atherogenic Diet ◽  
Negative Control ◽  
Positive Control Group ◽  
Control Group ◽  
Standard Diet ◽  
Sprague Dawley ◽  
Significant Difference

Abstract Background and aims: Cardiovascular diseases are widespread and causes many deaths in the world. The concentration of acute phase protein: C-reactive protein (CRP) and fibrinogen will rise dramatically when inflammation happens, which that can be used as an early marker of cardiovascular disease risk. Tempeh gembus contains fiber, unsaturated fatty acids and isoflavones are believed to reduce the inflammatory reaction. The aim of the study was to determinate the effect of tempeh gembus variations to levels of hcCRP and levels of fibrinogen of Sprague Dawley rats with atherogenic diet. Material and methods: This study was quasi-experimental with posttest only randomized control group design using 35 Sprague Dawley mice. The rats were randomized into 5 groups: negative control group given the standard diet, the positive control group given standard diet and atherogenic diet, and three treatment groups were given the standard diet, atherogenic diet and variation of tempeh gembus (tempeh gembus, heated tempeh gembus and tempeh gembus with bromelain enzyme) for 28 days. Serum levels of hsCRP and fibrinogen examined using ELISA (Enzyme-linked Immunosorbent Assay). Results and conclusions: The administration of tempeh gembus with bromelain enzyme is the most effective treatment for hsCRP serum level indicated a significant difference (p=0.028) between the negative control group, positive control group and first group with the third group. Fibrinogen serum levels showed significant differences in all treatment groups (p =0.042), administration of tempeh gembus with bromelain enzyme is the most effective treatment is shown by a significant difference between the negative control group and the positive control group with third group. The administration of tempeh gembus with bromelain enzyme for 28 days can reduce the serum levels of hsCRP and fibrinogen on rats significantly.

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