scholarly journals Subacute Oral Toxicity of Yukmijiwhang-Tang in Crl:CD Sprague-Dawley Rats and Its Cytotoxicity

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Soo-Jin Jeong ◽  
Chang-Seob Seo ◽  
Jung-Im Huh ◽  
Hyeun-Kyoo Shin
Keyword(s):  
Food Intake ◽  
Scientific Evidence ◽  
Safety Information ◽  
Clinical Signs ◽  
Serum Biochemistry ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Adverse Effect Level

Background. The traditional herbal formula Yukmijiwhang-tang (YMJ) consists of six medicinal herbs and has been used to treat dysuria, diabetic mellitus, and neurosis in Korea, China, and Japan. Here we report safety information on its subacute toxicity and the cytotoxicity.Methods. YMJ extract was administered to SD rats at various dosages for 4 weeks. We monitored clinical signs, mortality, body and organ weights, food intake, and hematological and serum biochemistry factors. For cytotoxicity testing, each cell line was treated with various concentrations of YMJ for 24 h.Results. YMJ treatment had no significant effects on changes in clinical signs, body weight, or food intake in male or female rats. In male rats, YMJ treatment decreased the absolute weights of the epididymides and serum Na levels. In female rats, YMJ significantly reduced the prothrombin time (PT) and serum creatine level. However, the changes were not severe and were considered to be in the normal physiological range for rats. The no-observed-adverse-effect-level (NOAEL) was estimated to be 2000 mg/kg/day. YMJ extract did not exert any cytotoxicity against 23 tested cell lines.Conclusions. Our data provide scientific evidence on the safety of YMJ for potential development as a prescription drug.

scholarly journals Acute and 30-day oral toxicity studies of a novel coccidiostat – ethanamizuril

2019 ◽  
Vol 8 (5) ◽  
pp. 686-695 ◽  
Author(s):  
Wenlong Xiao ◽  
Xiaoyang Wang ◽  
Chunmei Wang ◽  
Mi Wang ◽  
Chenzhong Fei ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Wall Thickening ◽  
High Dose ◽  
Alveolar Wall ◽  
Oral Toxicity ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Ld50 Value

Abstract Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity. Owing to its pharmacological properties, this study was conducted to evaluate the acute and 30-day oral toxicity of ethanamizuril. In the acute study, ethanamizuril was administered once by oral gavage to mice and rats. The calculated LD50 values for mice and rats were 5776 and 4743 mg per kg b.w, respectively, but the LD50 value for male rats was higher than that of female rats. In the subchronic study, male and female rats were fed with diets supplemented with 0, 20, 60 or 120 mg kg−1 ethanamizuril for 30 days. Treatment related clinical signs of alopecia on the back and neck of the animals were observed in the 60 and 120 mg kg−1 dose groups from the third week of treatment. Significant differences in haematological and biochemical parameters as well as organ-to-body weight ratios were detected between the 60 and 120 mg kg−1 groups. Histopathological observations revealed that 60 and 120 mg kg−1 ethanamizuril could induce focal hepatocellular necrosis and split phase. Slight renal tubule protein casts in the kidneys and alveolar wall thickening in the lungs were also observed in the high dose groups of both genders. The dietary no-observed-adverse-effect level (NOAEL) of ethanamizuril for 30 days was 20 mg kg−1 feed.

scholarly journals A 90-Day Oral Toxicity Study of the Ethanol Extract from Eupatorium japonicum Thunb and Foeniculum vulgare in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Guangcheng Dai ◽  
Chenglu Wang ◽  
Wei Tang ◽  
Jiangyun Liu ◽  
Boxin Xue
Keyword(s):  
Body Weight ◽  
Safety Information ◽  
Clinical Signs ◽  
Ethanol Extract ◽  
Male Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Foeniculum Vulgare ◽  
Hematological Indices ◽  
Eupatorium Japonicum

Eupatorium japonicum Thunb and Foeniculum vulgare are two of the most widely used folk herbs and constituents in many traditional Chinese herbal formulas. Nonetheless, little toxicological and safety information associated with following daily repeated exposure is obtained according to previous research. The present study was performed to assess the toxicity of ethanol extract from Eupatorium japonicum Thunb and Foeniculum vulgare (EFE) in male rats administered by dietary oral gavage at target doses of 0.39, 0.78, and 1.56 g/kg body weight/day for 90 days. There were no significant adverse effects on clinical signs, body weight, food conversion efficiency, and vital hematological indices. However, some hematology and biochemical indices such as WCV, MCH, MCHC, LY, MPV, T-CHO, as well as TG revealed significant changes in Sprague–Dawley rats and organ weights in lung and spleen showed diminished in male rats. Necropsy and histopathology findings suggested that no significant differences in absolute weights were found in all organs except lung and spleen, and no treatment-related alteration was identified in any organs. All results obtained in the present study indicated that the proper use of EFE in traditional medicine at oral dosages up to 1.56 g/kg/day body weight may harbor no prolonged toxicity to rats. However, further studies of EFE are still necessary to assess its oral safety in patients.

scholarly journals Subchronic and Genetic Safety Assessment of a New Medicinal Dendrobium Species: Dendrobium Taiseed Tosnobile in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Li-Chan Yang ◽  
Jiunn-Wang Liao ◽  
Chi-Luan Wen ◽  
Wen-Chuan Lin
Keyword(s):  
Histopathological Examination ◽  
Micronucleus Test ◽  
Clinical Signs ◽  
Serum Biochemistry ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Sd Rats

Dendrobium Taiseed Tosnobile is a new species of herba dendrobii (Shi-Hu) that was developed by crossbreeding D. tosaense and D. nobile. Its pharmacological activity and active component have been reported, but its subchronic toxicity and genetic safety have not yet been investigated. This study assessed the 90-day oral toxicity and genetic safety of the aqueous extracts of D. Taiseed Tosnobile (DTTE) in male and female Sprague-Dawley (SD) rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. DTTE was given orally to rats at 800, 1600, or 2400 mg/kg for 90 consecutive days, and distilled water was used for the control group. Genotoxicity studies were performed using a bacterial reverse mutation assay and in vivo mammalian cell micronucleus test in ICR mice and analyzed using flow cytometry. Throughout the study period, no abnormal changes were observed in clinical signs and body weight or on ophthalmological examinations. Additionally, no significant differences were found in urinalysis, hematology, and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. Based on results, the no-observed-adverse-effect level of DTTE is greater than 2400 mg/kg in SD rats.

scholarly journals A 4-Week Repeated Oral Dose Toxicity Study of Ssanghwa-Tang in Crl:CD Sprague Dawley Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Sae-Rom Yoo ◽  
Hyekyung Ha ◽  
Mee-Young Lee ◽  
Hyeun-kyoo Shin ◽  
Su-Cheol Han ◽  
...  
Keyword(s):  
Safety Information ◽  
Experimental Period ◽  
Serum Biochemistry ◽  
Toxicity Study ◽  
Herbal Formula ◽  
Sprague Dawley ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Ssanghwa-tang (SHT), a traditional herbal formula, has been widely used to recover fatigue or consumptive disease after an illness. Along with much attention to herbal formula, the concerns about the safety and toxicity have arisen. To establish the safety information, SHT was administrated in Crl:CD Sprague Dawley rats at a daily dose of 0, 1000, 2000, and 5000 mg/kg for 4 weeks. During the test periods, we examined the mortality, clinical observation, body weight change, food consumption, organ weights, hematology, serum biochemistry, and urinalysis parameters. No changes of mortality and necropsy findings occurred in any of the groups during the experimental period. In either sex of rats treated with SHT at 5000 mg/kg/day, changes were observed in food intake, reticulocyte, total bilirubin, some urinalysis parameters, and relative organ weights. The results indicated that SHT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. This dosage was considered no observed adverse effect level (NOAEL) and was appropriate for a 13-week subchronic toxicity study.

Studies of the Toxicological Potential of Capsinoids: VIII. A 13-Week Toxicity Study of Commercial-Grade Dihydrocapsiate in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 101-118 ◽  
Author(s):  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Food Consumption ◽  
Water Intake ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Organ Weights

Dihydrocapsiate, (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS No. 205687-03-2) is a naturally occurring capsinoid compound found in nonpungent chili peppers. Although the safety of synthetically produced dihydrocapsiate has been previously evaluated, the purpose of this 13-week gavage toxicity study is to evaluate dihydrocapsiate produced with a slightly modified manufacturing process. Sprague-Dawley rats, 10 rats/sex/group, 6 weeks of age at study initiation, were administered the dihydrocapsiate daily by gavage at dose levels of 0 (vehicle), 100,300, or 1000 mg/kg/day. The rats were observed for antimortem and postmortem signs of toxicity, including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. There were no changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, or blood chemistry that were attributable to the administration of dihydrocapsiate. The only change observed attributable to the dihydrocapsiate administration involved the liver and that change occurred only at the high dose (1000 mg/kg). Both sexes had an increase in organ weights, but this increase correlated with a change in histopathology (i.e., hepatocyte hypertrophy) only in the males. No dihydrocapsiate-related histopathological changes were observed in males at doses ≤300 mg/kg or in females at any of the doses tested (≤1000 mg/kg). It was concluded that the no observed adverse effect level (NOAEL) of dihydrocapsiate was 300 mg/kg/day for male rats and 1000 mg/kg/day for female rats in this 13 week gavage study.

scholarly journals A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sae-Rom Yoo ◽  
Hyekyung Ha ◽  
Mee-Young Lee ◽  
Hyeun-Kyoo Shin ◽  
Su-Cheol Han ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Serum Biochemistry ◽  
Toxicity Study ◽  
Repeated Dose ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Dose Oral

Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT), a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

The Subchronic Oral Toxicity of Ethane, 1,2-Bis(pentabromophenyl) (Saytex 8010) in Rats

2002 ◽  
Vol 21 (3) ◽  
pp. 165-170 ◽  
Author(s):  
M. L. Hardy ◽  
D. Margitich ◽  
L. Ackerman ◽  
R. L. Smith
Keyword(s):  
Corn Oil ◽  
Clinical Chemistry ◽  
Recovery Period ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Low Grade ◽  
Oral Toxicity ◽  
Effect Level

Ethane, 1,2-bis(pentabromophenyl) (EBP; CAS no. 8452–53–9) dose levels of 0, 100, 320 and 1000 mg/kg/day administered to rats by gavage in corn oil for 90 consecutive days produced no compound-related clinical signs of systemic toxicity, ocular lesions, or alterations in urinalysis, clinical chemistry, and hematology values in the treated or recovery groups. No biologically or toxicologically significant differences were observed in body weights, body weight gains, and food consumption. Statistically significant differences were found between control and high-dose animals in mean absolute or relative liver weights. Histomorphological evaluation showed in male rats low-grade liver changes consisting of minimal to slight hepatocellular vacuolation (high-dose males) and minimal to slight centrilobular hepatocytomegaly (high- and possibly mid-dose males). These changes had resolved by the end of the 28-day recovery period. No treatment-related changes were found in the livers of female rats. No treatment-related histomorphologic changes were present in any of the other tissues examined in either sex, except for evidence of aspirated test article in individual rats. The 90-day EBP no-adverse-effect level in the rat was 1000 mg/kg/day, and was consistent with that of the preceding 28-day study (no-effect level 1250 mg/kg/day). EBP's lack of toxicity is likely related to poor bioavailability due to its high molecular weight and low solubility.

scholarly journals Nutritional and 13-Week Subchronic Toxicological Evaluation of Lignosus rhinocerotis Mycelium in Sprague-Dawley Rats

2021 ◽  
Vol 18 (3) ◽  
pp. 1271
Author(s):  
I-Chen Li ◽  
Bi-Hua Yang ◽  
Jing-Yi Lin ◽  
Shan Lin ◽  
Chin-Chu Chen
Keyword(s):  
Body Weight ◽  
Histopathological Examination ◽  
Clinical Signs ◽  
Female Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Crude Lipid ◽  
Sprague Dawley Rats ◽  
Freeze Dried ◽  
Lignosus Rhinocerotis

Lignosus rhinocerotis (Tiger’s Milk mushroom) is a novel mushroom with sclerotium belonging to the Polyporaceae family and has been reported widely to possess anti-cancer, anti-cough, antioxidant, gastro-protective, immuno-modulating, and neurite-stimulating properties. As numerous studies have proven the tremendous medicinal values of L. rhinocerotis, it is necessary to understand its nutrition as well as its safety for the recipient. Previous research on L. rhinocerotis has mainly focused on the naturally occurring sclerotium and may have overlooked mushroom mycelia from submerged liquid fermentation, which ensures a high uniform quantitative biomass production as well as a high biological value. Hence, this is the first report on the evaluation of nutrition and 13-week repeated oral toxicity of L. rhinocerotis mycelium (LRM). The LRM powder contained 9.0 ± 4.2% moisture, 1.9 ± 1.3% ash, 1.6 ± 2.2% crude lipid, 8.4 ± 5.3% crude protein, 79.3 ± 4.6% carbohydrate, and 364 kcal/100 g energy. The total free amino acid ranged from 349 to 5636 mg/100 g and the umami index of freeze-dried LRM powder was 0.37. For safety assessment, ninety-six rats were divided into four groups, each consisting of twelve male and twelve female rats. Test articles were administered by oral gavage to rats at 850, 1700, and 3400 mg/kg body weight/day for 13 weeks and reverse osmosis water was used as the control. All animals survived to the end of the study. During the experiment period, no abnormal changes were observed in clinical signs, body weight, or ophthalmological examinations. No adverse or test article-related differences were found in urinalysis, hematology, or serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. According to the above results, the no-observed-adverse-effect level (NOAEL) of L. rhinocerotis was identified to be greater than 3400 mg/kg body weight (BW)/day in Sprague–Dawley rats.

scholarly journals Acute oral toxicity of squid and cuttlefish ink powder enzyme hydrolysates in Sprague-Dawley rats in accordance with the OECD Test Guideline 425

Food Research ◽  
2021 ◽  
Vol 5 (5) ◽  
pp. 259-264
Author(s):  
Ayu Shazwani Z. ◽  
Husnul Azan T. ◽  
Wan Ezumi M.F. ◽  
Rabeta M.S.
Keyword(s):  
Body Weight ◽  
Clinical Signs ◽  
Normal Structure ◽  
Female Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Sprague Dawley Rats ◽  
Behavioural Patterns ◽  
Ld50 Value ◽  
Enzyme Hydrolysate

The objectives of this study were to determine LD50 and establish the safety of ink squid and cuttlefish hydrolysates. In the acute toxicity study, three groups of female rats were randomly assigned. One group served as the control and two groups orally received a single limiting dose (2000 mg/kg body weight) of ink hydrolysates. There were no signs of adverse toxicity observed in behavioural patterns, clinical signs, and no significant differences (p>0.05) between the control and treated rats regarding their food and water consumption and body weight for up to 14 days. The histopathological evaluation revealed a normal structure and the absence of noticeable lesions in the vital organs of treated animals. It can be concluded that LD50 value is greater than 2000 mg/kg. The results showed that the squid ink powder enzyme hydrolysate (SIPEHs) and cuttlefish ink powder enzyme hydrolysate (CIPEHs) possess low toxicity, as indicated in the rat model. The preliminary results suggested that it should be further evaluated for long-term use and repeated dose effects to support the safe use of these hydrolysates.

Phosphorylation of STAT3 in hypothalamic nuclei is stimulated by lower doses of leptin than are needed to inhibit food intake

2021 ◽  
Author(s):  
Ruth B.S. Harris
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Random Order ◽  
Progressive Increase ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Hypothalamic Nuclei ◽  
Brown Adipose ◽  
Integrated Response

This experiment investigated which hypothalamic nuclei were activated by a dose of leptin that inhibited food intake. Food intake, energy expenditure, respiratory exchange ratio (RER) and intrascapular brown adipose tissue (IBAT) temperature were measured in male and female Sprague Dawley rats for 36 hours following an intraperitoneal injection of 0, 50, 200, 500 or 1000 mg leptin/kg with each rat tested with each dose of leptin in random order. In both males and females RER and 12 hour food intake and were inhibited only by 1000 mg leptin/kg, but there was no effect on energy expenditure or IBAT temperature. At the end of the experiment pSTAT3 immunoreactivity was measured one hour after injection of 0, 50, 500 or 1000 mg leptin/kg. In male rats the lowest dose of leptin produced a maximal activation of STAT3 in the Arc and nucleus of the solitary tract (NTS). There was no response in the dorsomedial hypothalamus but there was a progressive increase in VMH pSTAT3 with increasing doses of leptin. In female rats there was no significant change in Arc pSTAT3, NTS activation was maximal with 500 mg leptin/kg, but only the highest dose of leptin increased VMH pSTAT3. These results suggest that the VMH plays an important role in the energetic response to elevations of circulating leptin, but do not exclude the possibility that multiple nuclei provide the appropriate integrated response to hyperleptinemia.

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