scholarly journals Subchronic toxicity of lyophilized apoaequorin protein powder in Sprague-Dawley rats

2018 ◽  
Vol 2 ◽  
pp. 239784731875690
Author(s):  
Mark R. Bauter ◽  
Odete Mendes
Keyword(s):  
Active Ingredient ◽  
Calcium Binding ◽  
Clinical Pathology ◽  
Female Rats ◽  
Test Substance ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Dose Levels

Apoaequorin is a bioluminescent calcium-binding apoprotein endogenous to the Aequorea species of jellyfish and is commercially available in a dietary supplement in support of brain and cognitive health. Results from a previous 90-day subchronic oral gavage study established the no-observed-adverse-effect-level (NOAEL) of lyophilized apoaequorin protein powder (LAPP) at 666.7 mg/kg/day. The current 90-day oral gavage study in Sprague-Dawley rats administered dose levels of 1000, 2000, and 4000 mg/kg/day of test substance as received. These doses are expressed as milligram of supplement with the amounts of apoaequorin based on the analysis of the percentage of active ingredient. The corresponding amounts of apoaequorin protein are 603, 1206, and 2412 mg/kg/day. These dose levels target approximately 4221, 8442, and 16,844 times more than the expected human oral intake. There were no mortalities, clinical observations, ophthalmological, clinical pathology, or histopathological changes attributable to LAPP administration. Changes in mean body weight and feed efficiency, without other correlating clinical or pathological or other toxicologically relevant findings, were considered to be of little toxicological significance. Therefore, the NOAEL for LAPP administered orally up to 90 days was 4000 mg/kg/day (2412 mg/kg/day based on 603 mg/g or 60.3% active ingredient, apoaequorin protein), the highest dose tested in male and female rats.

scholarly journals A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

2016 ◽  
Vol 35 (5) ◽  
pp. 568-583 ◽  
Author(s):  
Palma Ann Marone ◽  
Jan Trampota ◽  
Steven Weisman
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Female Rats ◽  
Systemic Absorption ◽  
Test Substance ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

scholarly journals Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Ray A. Matulka ◽  
Ikuo Matsuura ◽  
Tohru Uesugi ◽  
Tomomi Ueno ◽  
George Burdock
Keyword(s):  
Developmental Toxicity ◽  
Bacterial Flora ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels ◽  
Reproductive Study

Consumption of the isoflavones daidzein, genistein, glycitein, and their structural analogues is generally considered beneficial to human health. Equol is not found in soy, but is converted from daidzein by human gut bacterial flora. Research indicates that between 30–50% of the population is capable of converting daidzein to equol; therefore, there has been recent development of a new equol-rich functional food that relies on bacterial conversion of daidzein to equol under strictly controlled conditions. Therefore, a new equol-rich soy product (SE5-OH) has been developed, based on the bacterial conversion of daidzein; and its reproductive and developmental toxicity has been evaluated in a two-generation study and a developmental toxicity study with Sprague-Dawley rats at dose levels of 200, 1000, and 2000 mg/kg/day by gavage. SE5-OH contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein, and 0.30% glycitein. From the reproductive study, the no-observed-adverse-effect-level (NOAEL) for SE5-OH determined for both male and female rats is 1000 mg/kg/day (6.5 mg equol/kg/day). In the developmental toxicity phase of the study, no effects by SE5-OH were found in the embryo-fetus at any of the doses tested. The NOAEL for developmental effects of SE5-OH is 2000 mg/kg/day (13 mg equol/kg/day).

scholarly journals Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

2018 ◽  
Vol 7 (5) ◽  
pp. 412-418
Author(s):  
Mohd Urooj ◽  
◽  
Mohammad Ahmed Khan ◽  
G. Thejaswini ◽  
Munawwar Husain Kazmi ◽  
...  
Keyword(s):  
Body Weight ◽  
Feed Intake ◽  
Clinical Signs ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Male And Female ◽  
Salix Caprea ◽  
Male And Female Rats ◽  
Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

scholarly journals Absorption, Distribution, Excretion, and Pharmacokinetics ofC-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Hyun Park ◽  
Kannampalli Pradeep
Keyword(s):  
Clinical Trials ◽  
Small Intestine ◽  
Oral Administration ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Phase Ii Clinical Trials ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Peak Value

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.

EFFECT OF NEONATAL ADMINISTRATION OF THYROXINE ON THE RATE OF SEBUM PRODUCTION IN RATS

1979 ◽  
Vol 83 (2) ◽  
pp. 199-203 ◽  
Author(s):  
YEE CHU TOH
Keyword(s):  
Normal Activity ◽  
Skin Surface ◽  
Postnatal Period ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Sebum Production ◽  
Skin Surface Lipids ◽  
Neonatal Administration

Newborn Sprague–Dawley rats of both sexes were treated with 28 μg thyroxine (T4) daily for the first week of life. At the age of 80 days, the secretion rate of sebum was measured from the amount of skin-surface lipids extractable by acetone and which had been produced during 2 days. Treatment with such excess amounts of T4 during the early postnatal period significantly reduced the production of sebum in both male and female rats when compared with control rats and with rats deprived of food early in life. The thyroid, the pituitary gland, the testes and the seminal vesicles were significantly smaller but the weights of the ovaries and uteri remained relatively unaffected. There was a similar ratio of sex difference in the rate of sebum secretion irrespective of treatment. It is suggested that a reduction of sebaceous response in rats made thyrotoxic with large doses of T4 early in life was probably due to a decreased secretion of thyroid hormone which is required to maintain normal activity of the sebaceous glands.

ROLE OF THE GONADS IN THE REGULATION OF SEBACEOUS GLANDS IN RATS: COMPARISON OF THE EFFECTS OF CASTRATION AT AND AFTER BIRTH

1980 ◽  
Vol 85 (2) ◽  
pp. 261-265 ◽  
Author(s):  
YEE CHU TOH
Keyword(s):  
Skin Surface ◽  
Female Rats ◽  
Sprague Dawley ◽  
Sebaceous Glands ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Sequential Event ◽  
Sebum Production ◽  
Skin Surface Lipids

Sprague–Dawley rats were castrated either within 24 h of birth or at 4 weeks of age. Control animals were sham operated. Intact female rats were also included for comparison. Sebum production was assessed at 80 days of age by measuring the amount of skin-surface lipids that could be extracted with acetone and which had been produced during 2 days. The removal of the testes at birth reduced the activity of the sebaceous glands to a level more nearly approaching that seen in the female rats whereas castration at 4 weeks of age only partially decreased the rate of sebum secretion so that it was intermediate between the male and female rats. The weights of the pituitary gland, thyroid and adrenal glands increased after castration but there were no differences between rats castrated at birth and those castrated at 4 weeks of age except in the weight of the thyroid gland. It would appear that the role of the testes in the control of the activity of the sebaceous glands is a sequential event which has already started at birth.

Lack of Oncogenicity of Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medication, in Sprague-Dawley Rats

2001 ◽  
Vol 20 (5) ◽  
pp. 297-305 ◽  
Author(s):  
Tomoo Kuge ◽  
Takashi Shibata ◽  
Michael S. Willett ◽  
Patricia Turck ◽  
Karl A. Traul
Keyword(s):  
Body Weight ◽  
Dose Level ◽  
Active Ingredient ◽  
Clinical Signs ◽  
Clinical Pathology ◽  
Maximum Tolerated Dose ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Wood Creosote

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021–39–4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

scholarly journals Intraperitoneal Alfaxalone and Alfaxalone–Dexmedetomidine Anesthesia in Sprague–Dawley Rats (Rattus norvegicus)

2020 ◽  
Vol 59 (5) ◽  
pp. 531-538
Author(s):  
Sylvia E West ◽  
Jonathan C Lee ◽  
Tinika N Johns ◽  
Elizabeth A Nunamaker
Keyword(s):  
Rattus Norvegicus ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Withdrawal Reflex ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Laboratory Rodent ◽  
Physiologic Parameters

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.

Abstract 386: Compound 21 Induces Natriuresis via Renal AT2 Receptor Activation in Male and Female Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
Robert M Carey
Keyword(s):  
Receptor Activation ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Angiotensin Iii ◽  
Compound 21 ◽  
Renal Cortical Interstitium

Endogenous renal des-aspartyl 1 -angiotensin II (angiotensin III) activates renal proximal tubule AT 2 receptors (AT 2 Rs) and induces natriuresis via a nitric oxide-cyclic GMP signaling pathway. The present study explores the ability of highly selective non-peptide AT 2 R agonist Compound 21 (C21) to induce natriuresis. Sprague-Dawley rats (12 weeks old; male N=22; female N=18) were studied in the presence and absence of concurrent 24-h AT 1 R blockade with candesartan (CAND;0.01 mg/kg/min). Rats were anesthetized with Inactin 100 mg/kg i.p., uninephrectomized and instrumented for delivery of 3 cumulative 30-min i.v. infusions of C21 (100, 200, and 300 ng/kg/min) following a 30-min control infusion of vehicle. Mean arterial pressure (MAP) was measured for all periods and urine Na + excretion rate (U Na V) was calculated for the control and final C21 collection periods. To determine whether the systemically induced natriuresis is mediated by renal AT 2 Rs, PD-123319 (PD), a specific AT 2 R antagonist, was infused directly into the renal cortical interstitium(20 μg/kg/min and 10 μg/kg/min for females and males, respectively) during the i.v. C21 infusions. In female rats, C21 increased U Na V from 1.5 ± 0.20 to 7.48 ± 0.95 μmol/min (P<0.0001). This response was abrogated by concurrent intrarenal PD infusion [control 0.74 ± 0.19 vs. C21 2.02 ± 0.50 μmol/min (P<0.001from C21 alone). Systemic CAND administration augmented the natriuretic response to C21 [control 1.29 ± 0.25 vs. C21 10.68 ± 0.70 μmol/min (P<0.05 from C21 alone)]. In male rats, C21 increased U Na V from 0.46 ±0.08 to 6.21 ± 1.33 μmol/min (P<0.01). This response was blocked by concurrent intrarenal PD infusion [control 0.39 ± 0.11 vs. C21 1.69 ± 0.53 μmol/min (P<0.05 from C21 alone). Systemic CAND did not significantly alter the natriuretic response to C21 alone [control 0.49 ± 0.15 vs. C21 7.67 ± 0.72 μmol/min (P = NS from C21 alone). In female rats, CAND augmented the natriuretic response to C21 over that of male rats (P<0.01). Systemic arterial pressures were decreased by CAND in both male and female rats but were unchanged by C21 alone or together with intrarenal PD. C21 induces natriuresis via renal AT 2 R activation in both male and female rats. These data suggest the potential for AT 2 R agonist therapy in hypertension.

Maximum oxygen consumption of rats and its changes with various experimental procedures

1979 ◽  
Vol 47 (6) ◽  
pp. 1278-1283 ◽  
Author(s):  
T. G. Bedford ◽  
C. M. Tipton ◽  
N. C. Wilson ◽  
R. A. Oppliger ◽  
C. V. Gisolfi
Keyword(s):  
Test Procedure ◽  
Repeated Measurements ◽  
Female Rats ◽  
Shr Rats ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto ◽  
Different Strains

A ten-stage treadmill test was developed and standardized to secure the VO2max of male and female rats assigned to various cross-sectional and longitudinal experimental groups. Repeated measurements indicated that the test procedure was reliable and could be used for research purposes. When the test was used with different strains, the untrained Sprague-Dawley rats had significantly higher VO2max values than animals of the Wistar-Kyoto (WKY) or the Okamoto-Aoki (SHR) strains. Exercise schedules were evaluated that were similar to those previously used by various investigators and it was found that most were exercising their rats at levels exceeding 75% VO2max. After 6--10 wk of chronic exercise, significant increases in VO2max occurred that ranged between 12 and 26%. Longitudinal studies (1 yr) with hypertensive (SHR) rats revealed that it was more desirable to logarithmically evaluate the relationship between VO2max and body mass than by the conventional method of ml . kg-1 . min-1. When this approach was used with SHR animals, the VO2max differences between the sexes were not apparent until the animals were 1 yr of age. On the other hand, training by male SHR rats caused significant increases in VO2max regardless of the method used to express the results. It is recommended that future studies designed to elucidate exercise mechanisms in rats should include a standardized VO2max test.

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