Non-toxic nature of chebulinic acid on biochemical, hematological and histopathological analysis in normal Sprague Dawley rats

Unsweetened natural cocoa powder (UNCP) is a pulverized high-grade powder of compressed solid blocks which remains after extraction. Little scientific data is available concerning its safety despite the presence of potential toxic elements. Elemental composition in UNCP was analyzed with ED-XRF spectroscopy. Single oral high dose toxicity study was conducted on adult male Sprague-Dawley rats (150 g) by the limit test method. One group received water and the test group 2000 mg/kg UNCP. All animals were observed for 14 days and then euthanized for haematological, biochemical, and histopathological examinations. Thirty-eight (38) elements were found in UNCP. There was an increase in HDL cholesterol (p<0.05), reduction in LDL cholesterol (p>0.05), alkaline phosphatase (p<0.05), and creatinine levels, and slight increase in urea levels (p>0.05). Haematological changes were not significant. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Intestinal erosion was observed in the test group. UNCP appears to be relatively safe when taken as a single oral high dose of 2000 mg/kg b.w.t. in rats. Caution should however be exercised at high doses due to the high elemental content of copper and high possibility of intestinal lining erosion.

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Toxicogenomic Analysis of Cardiotoxicity in Rats

Genomics Insights ◽

10.4137/gei.s851 ◽

2008 ◽

Vol 1 ◽

pp. GEI.S851 ◽

Cited By ~ 5

Author(s):

Brad Hirakawa ◽

Bart A. Jessen ◽

Oscar Illanes ◽

Ann de Peyster ◽

Thomas McDermott ◽

...

Keyword(s):

Gene Expression ◽

Carbon Tetrachloride ◽

Rapid Assessment ◽

Negative Control ◽

Histopathological Analysis ◽

Sprague Dawley ◽

Post Dose ◽

Sprague Dawley Rats ◽

Control Compound

Evidence of cardiotoxicity in the preclinical testing of drugs will often lead to compound attrition. The standard method for identifying cardiotoxic compounds involves histopathological analysis of tissue sections, a resource intensive process. In an effort to reduce attrition and capture safety endpoints early within the drug discovery paradigm, a more rapid assessment of target organ effects is desired. Here we describe the results of a preliminary study in which a group of common genes were affected by in vivo exposure to compounds known to cause dose-dependant cardiotoxicity. Adult male Sprague-Dawley rats were treated intraperitoneally with a single dose of digoxin (20 mg/kg), doxorubicin (30 mg/kg), isoproterenol (70 mg/kg), lipopolysaccharide (10 mg/kg) or carbon tetrachloride (800 mg/kg) and euthanized either 6 or 24 hours post-dose. Digoxin, doxorubicin, isoproterenol, and lipopolysaccharide were chosen for this study based on their diverse mechanisms of cardiotoxicity. Carbon tetrachloride, a known liver toxicant, was chosen as a non-cardiotoxic negative control. Genes commonly affected by all four cardiotoxic compounds were grouped together as a list of potential biomarkers. Gene expression changes were subsequently quantified using quantitative PCR. These genes were compared to those affected by novel experimental compounds previously shown to cause cardiotoxicity in rats. These compounds also affected over half of the genes on the biomarker list, whereas the non-cardiotoxic control compound did not affect any genes on the biomarkers list. These data indicate that measuring changes in gene expression could aid in the prioritization of compounds before they are tested in more resource intensive studies.

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Hepatoprotection by Freshwater Clam Extract Against CCl4-Induced Hepatic Damage in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x10008329 ◽

2010 ◽

Vol 38 (05) ◽

pp. 881-894 ◽

Cited By ~ 27

Author(s):

Chin-Lin Hsu ◽

Chien-Chen Hsu ◽

Gow-Chin Yen

Keyword(s):

Thiobarbituric Acid ◽

Serum Levels ◽

Hepatoprotective Effect ◽

Histopathological Analysis ◽

Sprague Dawley ◽

Injury Score ◽

Freshwater Clam ◽

Sprague Dawley Rats ◽

Alternative Approach ◽

Serum Biochemical

Freshwater clam is traditionally used as a food and has been mentioned in ancient books to have a hepatoprotective effect. The hepatoprotective effect of freshwater clam extract was evaluated in the model of chronic hepatic fibrosis induced by carbon tetrachloride ( CCl4 ). Male Sprague-Dawley rats were orally treated with freshwater clam extract (0.3, 0.6 and 1.5 g/kg of bw) or silymarin (0.2 g/kg of bw) along with the administration of CCl4 (0.5 ml/rat, 20% CCl4 in olive oil) for eight consecutive weeks. Blood samples were collected for assaying serum biochemical parameters. The livers were excised for evaluating peroxidation products and antioxidant substances, as well as the activities of antioxidant enzymes. Pathological histology was also performed. The data showed that supplementation of freshwater clam extract (0.6 g/kg bw) significantly reduced the serum levels of alanine aminotransferase and aspartate aminotransferase in rats treated with CCl4 , and also decreased the thiobarbituric acid reactive substances, hydroxyproline and excessive inflammation in the livers of CCl4 -treated rats. Histopathological analysis of the liver showed that freshwater clam extract (0.6 g/kg bw) markedly reduced the injury score of the fibrosis induced by CCl4 in rats. The data suggest that oral administration with freshwater clam extract might provide a novel and alternative approach for treating chronic liver failure.

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Acute Wound Healing Potential of Marine Worm, Diopatra claparedii Grube, 1878 Aqueous Extract on Sprague Dawley Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6688084 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Nor ‘Awatif Che Soh ◽

Hannah Syahirah Rapi ◽

Nurul Shahirah Mohd Azam ◽

Ramesh Kumar Santhanam ◽

Suvik Assaw ◽

...

Keyword(s):

Wound Healing ◽

Aqueous Extract ◽

Microbial Contamination ◽

Skin Irritation ◽

Antibacterial Activities ◽

Histopathological Analysis ◽

Sprague Dawley ◽

Local Skin ◽

Sprague Dawley Rats ◽

Acute Wound

Diopatra claparedii which is colloquially known as Ruat Sarung can be found along the west coast of Peninsular Malaysia. The species has a unique ability to regenerate anterior and posterior segments upon self-amputation or injury, thus having potential as a wound healing promoter. In this study, the wound healing potential of D. claparedii aqueous extract on acute wound model in rats was revealed for the first time. Various concentrations (0.1%, 0.5%, and 1.0% w/w) of D. claparedii ointment were formulated and tested on Sprague Dawley rats through topical application on full-thickness skin wounds for 14 days. The wound healing effects were investigated via behaviour observation, wound contraction, and histopathological analysis. Quality assessment was performed via skin irritation test, microbial contamination test (MCT), and heavy metal detection. The study also included test for antibacterial activities and detection of bioactive compounds in D. claparedii. One percent of D. claparedii ointment showed rapid wound healing potential with good soothing effects and more collagen deposition in comparison to the commercial wound healing ointments such as acriflavine (0.1% w/v) and traditional ointment gamat (sea cucumber extract) (15.0% w/v). No local skin irritation, microbial contamination, and insignificant concentration of heavy metals were observed, which indicate its safe application. Moreover, the aqueous extract of D. claparedii exhibited antibacterial activities against Escherichia coli and Pseudomonas aeruginosa with minimum inhibitory concentration (MIC) value at 0.4 g/ml. 1H NMR analysis of the aqueous extract of D. claparedii revealed some metabolites that might be responsible for its wound healing properties such as amino acids, halogenated aromatics, organic acids, vitamins, and others. Altogether, these results suggested that the aqueous extract of D. claparedii could be utilised as an alternative natural wound healing promoter.

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Oral toxicity of arjunolic acid on hematological, biochemical and histopathological investigations in female Sprague Dawley rats

PeerJ ◽

10.7717/peerj.8045 ◽

2019 ◽

Vol 7 ◽

pp. e8045 ◽

Cited By ~ 3

Author(s):

Khurram Aamir ◽

Hidayat Ullah Khan ◽

Chowdhury Faiz Hossain ◽

Mst. Rejina Afrin ◽

Imam Shaik ◽

...

Keyword(s):

Body Weight ◽

Safety Profile ◽

Periodic Acid ◽

Scientific Data ◽

In Vivo Studies ◽

Histopathological Analysis ◽

Normal Female ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Arjunolic Acid

Background Arjunolic acid (AA) is a potent phytochemical with wider pharmacological activities. Despite potential medicinal properties on various in vitro and in vivo studies, there is still a dearth of scientific data related to its safety profile and toxicological parameters. The current study aimed to investigate acute toxicity of AA in normal female Sprague Dawley rats. Methods In this study, AA was administered orally at an individual dose of 300 and 2000 mg/kg body weight to group 1 and 2 respectively, while group 3 served as normal control. All the animals were observed for 2 weeks to determine any behavioral and physical changes. On day 15, blood was collected for hematological and biochemical investigation, later animals from all the three groups were euthanized to harvest and store essential organs for histopathological analysis. Four different staining techniques; hematoxylin and eosin, Masson trichrome, Periodic acid Schiff and Oil O Red were used to investigate any alterations in different tissues through microscopical observation. Results The results of the study showed no morbidity and mortality at two different dosage of AA treatment. Daily food & water intake, body weight, relative organ weight, hematological and biochemical parameters were detected to be normal with no severe alteration seen through microscopical investigation in the structure of harvested tissues. Our findings support the safety profile of AA, which was well tolerated at higher dose. Thus, an in-detail study on the subacute disease model is warranted.

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Evaluation of acute and sub-acute oral toxicity of the aqueous extract of Aquilaria malaccensis leaves in Sprague Dawley rats

Asia Pacific Journal of Molecular Biology and Biotechnology ◽

10.35118/apjmbb.2019.027.1.03 ◽

2019 ◽

pp. 20-32

Author(s):

Redzuan Nul Hakim Abdul Razak ◽

Suzanah Abdul Rahman ◽

Asmah Hanim Hamdan ◽

Roszaman Ramli ◽

Muhammad Lokman Md Isa ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Lethal Dose ◽

The Body ◽

Female Rats ◽

Male Rats ◽

Histopathological Analysis ◽

Sprague Dawley ◽

Aquilaria Malaccensis ◽

Sprague Dawley Rats

Aquilaria malaccensis or commonly known as ‘gaharu’ is a species of Aquilaria genus and belongs to the Thymelaeaceae family. It is widely distributed in Malaysia, Indonesia, and the Borneo Islands. Traditionally, its leaves were used to relieve bruises and studies have shown that they function as an antioxidant, aphrodisiac, and tranquilizer. Despite its proven beneficial medicinal properties, information regarding its toxicity is limited. Therefore, we performed a safety evaluation on the aqueous A. malaccensis leaves extract (AMAE) in Sprague Dawley rats. The assessment of acute toxicity based on the Organization for Economic Cooperation and Development (OECD) Guideline 420 revealed that AMAE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 2000 mg/kg body weight. In the sub-acute toxicity, all doses did not significantly modify the body weight and food and water intake. In male rats treated with 2000 mg/kg, there was a significant reduction in the relative weight of liver. Not only that, an increase in alkaline phosphatase and alanine transaminase was also observed in different groups among the female rats. A significant decrease in the creatinine level was also seen among male rats administered with different doses of AMAE. In both sexes, histopathological analysis had shown abnormalities in the liver and kidney of rats treated at the dose of 2000 mg/kg. In conclusion, the 50% lethal dose (LD50) of AMAE was estimated to be greater than 2000 mg/kg. In sub-acute duration, the findings suggested that AMAE administered orally is slightly toxic at higher doses (2000 mg/kg) and could provoke functional and structural changes in the kidney and liver of rats. Thus, the extract should be used with caution.

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Ultrastructural Investigation of Spontaneous Pituitary Adenomas in Aging Sprague-Dawley Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053747 ◽

1982 ◽

Vol 40 ◽

pp. 216-217

Author(s):

D. J. McComb ◽

J. Beri ◽

F. Zak ◽

K. Kovacs

Keyword(s):

Microscopic Study ◽

Pituitary Adenomas ◽

Wistar Rats ◽

Microscopic Level ◽

Sprague Dawley ◽

Prolactin Cells ◽

Light Microscopic Level ◽

Ultrastructural Investigation ◽

Sprague Dawley Rats ◽

Long Evans

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.

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Early Development of Drug-Induced Hepatic Necrosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066942 ◽

1971 ◽

Vol 29 ◽

pp. 576-577

Author(s):

F. G. Zaki ◽

E. Detzi ◽

C. H. Keysser

Keyword(s):

Early Development ◽

Hepatic Necrosis ◽

Screening Tests ◽

Dense Matrix ◽

Sprague Dawley ◽

Electron Microscopic ◽

Drug Induced ◽

Hepatocellular Damage ◽

Sprague Dawley Rats ◽

Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077086 ◽

1983 ◽

Vol 41 ◽

pp. 702-703

Author(s):

D. J. McComb ◽

J. Beri ◽

F. Zak ◽

K. Kovacs

Keyword(s):

Electron Microscopy ◽

Animal Model ◽

Epoxy Resin ◽

Immunoelectron Microscopy ◽

Tumor Type ◽

Gonadal Function ◽

Sprague Dawley ◽

Male And Female ◽

Reticulin Fibers ◽

Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

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Freeze-etch studies of epiphyseal growth plate cartilage reveal matrix vesicles associated with calcification

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084223 ◽

1978 ◽

Vol 36 (2) ◽

pp. 670-671

Author(s):

Russell N. A. Cecil ◽

H. Clarke Anderson

Keyword(s):

Chromic Acid ◽

Light And Electron Microscopy ◽

Matrix Vesicles ◽

Matrix Vesicle ◽

Glycerol Solution ◽

Sprague Dawley ◽

Epiphyseal Growth Plate ◽

Growth Plates ◽

Sprague Dawley Rats ◽

Tibial Epiphyseal

Unfixed proximal tibial epiphyseal growth plates were studied by freeze-etch to confirm the presence of extracellular calcifying matrix vesicles and to determine the substructure of matrix vesicle membranes as compared to plasma and other membranes of intact chondrocytes. Growth plates from 6-10 week old Sprague-Dawley rats were cut into 1x3 mm blocks whose long dimension was oriented either perpendicular or parallel to the long axis of the tibia. Some blocks were fixed at pH 7. 0 in 0. 2M cacodylate - buffered 2. 5% glutaraldehyde for 1 hour at 4ÅC. The blocks were immersed in 30% glycerol solution at 4ÅC for 1 hour, frozen in liquid nitrogen, and then fractured, etched for 2 minutes, and coated with platinum, carbon and 0. 2% Formvar solution. The replicas were cleaned with chromic acid, floated onto Formvar coated grids, and examined with a Phillips EM 300 electron microscope.Fixed and unfixed specimens appeared similar in ultrastructure. Chondrocytes, matrix, and matrix vesicles were identified. In specimens fractured parallel to the long axis of the tibia, the reserve, proliferative, hypertrophic, and calcifying zones could be discerned as described by light and electron microscopy.

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