Pharmacokinetics of bio-shell-silver-core nanoparticles (AgNP) in Sprague-Dawley Rats – In vivo study

2021 ◽  
Vol 09 ◽  
Author(s):  
Asra Parveen ◽  
Vijay kumar B. Malashetty ◽  
Sushruta Marla ◽  
Shanth Reddy ◽  
Sidramappa Sirsand ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Body Weight ◽  
Biomedical Applications ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Potential Toxicity ◽  
Target Organs ◽  
Sprague Dawley Rats

Background: Silver nanoparticles have been widely used in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. Objectives: The purpose of this study was to investigate the safety of silver nanoparticles by determining its potential toxicity following 28 days administration in Sprague Dawley rats. Method: The silver nanoparticles were administered by intravenous injection at the doses of 100, 200 and 500 µg/kg body weight for 28 consecutive days. Animals in the control group were received sterile water for injection. Each group consists of 10 male and 10 female rats. Results: No treatment related effects were seen in any of the parameters monitored in rats given 100, 200 and 500 µg/kg body weight/day of silver nanoparticles. Conclusion: The study proved that the use of up to 500 µg/kg body weight biosynthesized silver nanoparticles have no toxic effect in the target organs and found safe. However, the safety of the nanoparticles might be attributed to the covering of biological moieties on nanoparticles. Hence, the biofunctionalized nanoparticles can be safely used by selecting the required size and dose in medicines and drug delivery systems.

SUBCHRONIC TOXICITY OF MALAYSIAN ACALYPHA INDICA: BIOCHEMISTRY AND HAEMATOLOGY ANALYSIS OF RAT

2016 ◽  
Vol 78 (5-5) ◽  
Author(s):  
Norazlanshah Hazali ◽  
Nurul Nadia Mohd Nazri ◽  
Muhammad Ibrahim ◽  
Mashita Masri
Keyword(s):  
Body Weight ◽  
Skin Diseases ◽  
Female Rats ◽  
Control Group ◽  
Dosage Group ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
High Dosage Group ◽  
Sprague Dawley Rats ◽  
Acalypha Indica

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.

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.

Dosimetry and pathology of 237Np in female rats

1997 ◽  
Vol 16 (2) ◽  
pp. 89-100 ◽  
Author(s):  
W. Sontag ◽  
R. Wirth ◽  
A. Luz ◽  
E. Schäffer ◽  
V. Volf
Keyword(s):  
Body Weight ◽  
Life Span ◽  
The Body ◽  
Female Rats ◽  
Whole Body ◽  
Pathological Examination ◽  
Control Group ◽  
Sprague Dawley ◽  
Weight Group ◽  
Sprague Dawley Rats

Female Sprague-Dawley rats, 10-12-week old and weigh ing about 240 g, were injected intravenously with 237Np nitrate. In the toxicological study 77 rats served as controls and 28 rats per group received single doses of 5.2 and 26 kBq, respectively, per kg body weight. In addition, 12 rats of each injection level, sacrificed at defined points in time, were used for dosimetric studies. During the whole life-span the body weight and 237Np whole body-content of each animal were recorded. After death a detailed pathological examination was made of each animal in the cronical study. One day after injection 48% of the injected activity was in the skeleton, 9.3% in the liver, 3% in the kidneys and 4.4% in the rest of the organs. Whereas in all organs the activity decreased very fast, the half-life in the skeleton was about 1400 days. The bodyweights were comparable in the three groups, but the life span decreased from 800 days (control group) to 644 days after injection (26 kBq kg -1 body weight group). The main lesions in the female rats were mammary tumors (73%) and pituitary gland tumors (52%). With increasing activity the incidence of pituary gland tumors decreased and that of osteosarco mas increased from 1.3% (control group) to 32% (26 kBq kg-1 body weight group), whereas the remaining lesions showed no influence on the activity.

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 Greater natriuretic response to ENaC inhibition in male versus female Sprague-Dawley rats

2020 ◽  
Vol 318 (2) ◽  
pp. R418-R427 ◽  
Author(s):  
Reham H. Soliman ◽  
Jermaine G. Johnston ◽  
Eman Y. Gohar ◽  
Crystal M. Taylor ◽  
David M. Pollock
Keyword(s):  
Protein Expression ◽  
Time Of Day ◽  
Female Rats ◽  
Female Rat ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Endothelin System ◽  
Males And Females ◽  
Epithelial Sodium Channel Enac

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber time 0 (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical α-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na+ balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.

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.

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 A Novel Strategy to Enhance Microfracture Treatment With Stromal Cell-Derived Factor-1 in a Rat Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Taylor Mustapich ◽  
John Schwartz ◽  
Pablo Palacios ◽  
Haixiang Liang ◽  
Nicholas Sgaglione ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cartilage Repair ◽  
Osteochondral Defect ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stromal Cell Derived Factor ◽  
Empty Control

BackgroundMicrofracture is one of the most widely used techniques for the repair of articular cartilage. However, microfracture often results in filling of the chondral defect with fibrocartilage, which exhibits poor durability and sub-optimal mechanical properties. Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for mesenchymal stem cells (MSCs) and is expressed at high levels in bone marrow adjacent to developing cartilage during endochondral bone formation. Integrating SDF-1 into an implantable collagen scaffold may provide a chondro-conductive and chondro-inductive milieu via chemotaxis of MSCs and promotion of chondrogenic differentiation, facilitating more robust hyaline cartilage formation following microfracture.ObjectiveThis work aimed to confirm the chemoattractive properties of SDF-1 in vitro and develop a one-step method for incorporating SDF-1 in vivo to enhance cartilage repair using a rat osteochondral defect model.MethodsBone marrow-derived MSCs (BMSCs) were harvested from the femurs of Sprague–Dawley rats and cultured in low-glucose Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum, with the medium changed every 3 days. Passage 1 MSCs were analyzed by flow cytometry with an S3 Cell Sorter (Bio-Rad). In vitro cell migration assays were performed on MSCs by labeling cells with carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE; Bio-Rad). For the microfracture model, a 1.6-mm-diameter osteochondral defect was created in the femoral trochleae of 20 Sprague–Dawley rats bilaterally until bone marrow spillage was seen under saline irrigation. One knee was chosen at random to receive implantation of the scaffold, and the contralateral knee was left unfilled as an empty control. Type I collagen scaffolds (Kensey Nash) were coated with either gelatin only or gelatin and SDF-1 using a dip coating process. The rats received implantation of either a gelatin-only scaffold (N = 10) or gelatin-and-SDF-1 scaffold (N = 10) at the site of the microfracture. Femurs were collected for histological analyses at 4- and 8-week time points post-operatively, and sections were stained with Safranin O/Fast Green. The samples were graded blindly by two observers using the Modified O’Driscoll score, a validated scoring system for chondral repair. A minimum of 10 separate grading scores were made per sample and averaged. Quantitative comparisons of cell migration in vitro were performed with one-way ANOVA. Cartilage repair in vivo was also compared among groups with one-way ANOVA, and the results were presented as mean ± standard deviation, with P-values < 0.05 considered as statistically significant.ResultsMSC migration showed a dose–response relationship with SDF-1, with an optimal dosage for chemotaxis between 10 and 100 ng/ml. After scaffold implantation, the SDF-1-treated group demonstrated complete filling of the cartilage defect with mature cartilage tissue, exhibiting strong proteoglycan content, smooth borders, and good incorporation into marginal cartilage. Modified O’Driscoll scores after 8 weeks showed a significant improvement of cartilage repair in the SDF-1 group relative to the empty control group (P < 0.01), with a trend toward improvement when compared with the gelatin-only-scaffold group (P < 0.1). No significant differences in scores were found between the empty defect group and gelatin-only group.ConclusionIn this study, we demonstrated a simple method for improving the quality of cartilage defect repair in a rat model of microfracture. We confirmed the chemotactic properties of SDF-1 on rat MSCs and found an optimized dosage range for chemotaxis between 10 and 100 ng/ml. Furthermore, we demonstrated a strategy to incorporate SDF-1 into gelatin–collagen I scaffolds in vivo at the site of an osteochondral defect. SDF-1-treated defects displayed robust hyaline cartilage resurfacing of the defect with minimal fibrous tissue, in contrast to the empty control group. The results of the in vitro and in vivo studies together suggest that SDF-1-mediated signaling may significantly improve the quality of cartilage regeneration in an osteochondral defect.

scholarly journals Histological and biochemical effects of Cinnamomum cassia nanoparticles in kidneys of diabetic Sprague-Dawley rats

2019 ◽  
Author(s):  
Koffi Kouame ◽  
Aniekan Imo Peter ◽  
Edidiong Nnamso Akang ◽  
Roshila Moodley ◽  
Edwin Coleridge Naidu ◽  
...  
Keyword(s):  
Body Weight ◽  
Fasting Blood Glucose ◽  
Kidney Tissue ◽  
Saline Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Cinnamomum Cassia ◽  
Sprague Dawley Rats ◽  
Group A ◽  
Group B

This study investigated the antidiabetic activity of Cinnamomum cassia (C. cassia, Cc) silver nanoparticles (CcAgNPS) and effects of C. cassia on the kidneys of rats with induced type 2 diabetes. Twenty-four Sprague-Dawley rats weighing 250 ± 20 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Animals were randomly assigned to one of four groups (n = 6) and treated for eight weeks with normal saline (control, group A), 5 mg/kg of CcAgNPs (group B), 10 mg/kg of CcAgNPs (group C), or 200 mg/kg of Cc (group D). Body weight and fasting blood glucose (FBG) was measured weekly and fortnightly, respectively. At the end of experiments, animals were euthanized, blood and kidney tissue samples were collected for biochemistry (oxidative stress markers and renal function parameters) and kidneys were harvested for histology (PAS and HE staining). Body weight was significantly higher in group B and C vs. control (p < 0.05), while no significant differences were observed in the kidney-to-body weight ratio between groups. FBG, glutathione, malondialdehyde, alanine aminotransferase, aspartate aminotransferase, serum urea and creatinine were significantly lower in group B, C and/or D vs. control (all p < 0.05). In group A, severe distortion of the glomerular network was observed, marked by the loss of capsular integrity, thickened basement membrane, tubular cells with pyknotic nuclei, vacuolization, and interstitial space with infiltrations. These adverse effects were mitigated by 5 mg/kg and 10 mg/kg of CcAgNPs. Our study confirms structural and functional damage to kidneys caused by diabetes. CcAgNPs have a regenerative potential in diabetes-induced kidney damage and may be used as an antidiabetic agent.

scholarly journals 7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse
Keyword(s):  
Body Weight ◽  
Progressive Ratio ◽  
Ethanol Exposure ◽  
Ethanol Solution ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Self Administration ◽  
Bdnf Expression ◽  
Sprague Dawley Rats

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.

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