Early Development of Drug-Induced Hepatic Necrosis

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.

Light and electron microscopic investigation of adenohypophyses of germfree, food-restricted, and germfree-food restricted aging, male lobund-wistar rats

1988 ◽  
Vol 46 ◽  
pp. 352-353
Author(s):  
G. Ilse ◽  
K. Kovacs ◽  
N. Ryan ◽  
T. Sano ◽  
L. Stefaneanu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Microscopic Investigation ◽  
Electron Microscopic Investigation ◽  
Aging Male ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Sprague Dawley Rats ◽  
Old Rats ◽  
Ad Libitum ◽  
Microscopic Findings

Germfree state and food restriction have been shown to increase life span and delay tumor occurrence in rats. We report here the histologic, immunocytochemical and electron microscopic findings of adenohypophyses of aging, male Lobund-Wistar rats raised at Lobund Laboratories. In our previous study, the morphologic changes in the adenohypophyses of old rats have been extensively investigated by histology, immunocytochemistry and electron microscopy. Lactotroph adenomas were frequent in Long-Evans and Sprague-Dawley rats, whereas gonadotroph adenomas were frequent in Sprague-Dawley and Wistar rats.Male Lobund-Wistar rats were divided into four groups: 1) conventional, which were raised under normal non-germfree environment and received food ad libitum; 2) germfree-food ad libitum; 3) conventional environment-food restricted and 4) germfree-food restricted. The adenohypophyses were removed from 6-month-, 18-month- and 30-month-old rats. For light microscopy, adenohypophyses were fixed in formalin and embedded in paraffin.

The Hepatoprotective Role of Warburgia salutaris and Iso-Mukaadial Acetate on Carbon tetrachloride Intoxicated Rats Model

2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Injury ◽  
Antioxidant Properties ◽  
Hepatic Necrosis ◽  
Protective Role ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Isolated Compound

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.

scholarly journals Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy

2016 ◽  
Vol 45 (2) ◽  
pp. 344-352 ◽  
Author(s):  
Michael E. Dunn ◽  
Thomas G. Manfredi ◽  
Kevin Agostinucci ◽  
Steven K. Engle ◽  
Josh Powe ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Left Ventricular ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sprague Dawley Rats ◽  
Exercise Induced

Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

Preclinical assessment of tramadol abuse potential: Effects of acute and repeated tramadol on intracranial self-stimulation in rats

2020 ◽  
Vol 34 (11) ◽  
pp. 1316-1325
Author(s):  
Ahmad A Altarifi ◽  
Megan J Moerke ◽  
Mohammad I Alsalem ◽  
S Stevens Negus
Keyword(s):  
Enzyme Inhibitor ◽  
Abuse Potential ◽  
Opioid Antagonist ◽  
Repeated Treatment ◽  
Acute Administration ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Self Stimulation

Background: Tramadol is a widely used analgesic that activates mu-opioid receptors (MOR) and inhibits serotonin and norepinephrine transporters. This mixed pharmacology may limit both its own abuse potential and its modulation of abuse potential of other MOR agonists. Aims: This study used an intracranial self-stimulation (ICSS) procedure to compare abuse-related effects produced by acute or repeated treatment with tramadol or morphine in rats. Abuse potential in ICSS procedures is indicated by a drug-induced increase (or ‘facilitation’) of ICSS responding. Methods: Adult male Sprague–Dawley rats were implanted with electrodes targeting the medial forebrain bundle and trained to respond on a lever for pulses of electrical brain stimulation. Tramadol effects were evaluated after acute administration (3.2–32 mg/kg) in the absence or presence of the opioid antagonist naltrexone, the CYP2D6 hepatic-enzyme inhibitor quinine or a combination of both. Additionally, both tramadol and morphine were also tested before and after repeated tramadol (32 mg/kg/day for six days) or repeated morphine (3.2 mg/kg/day for six days). Results: Acute tramadol produced primarily ICSS rate-decreasing effects that were antagonised by naltrexone but not by quinine or naltrexone + quinine. Tramadol also produced little or no ICSS facilitation after repeated tramadol or repeated morphine, and repeated tramadol did not enhance ICSS facilitation by morphine. By contrast, morphine-induced ICSS facilitation was enhanced by repeated morphine treatment. Conclusions: These results suggest that tramadol has lower abuse potential than other abused MOR agonists and that repeated tramadol exposure produces relatively little enhancement of abuse potential of other MOR agonists.

Effect of Streptozotocin-Induced Diabetes on Estradiol-Stimulated Changes in the Ultrastructure of the Rat Endometrium

1981 ◽  
Vol 39 ◽  
pp. 532-533
Author(s):  
G.T. Frederick ◽  
R.M. Gardner ◽  
J.M. Kirkland ◽  
G.M. Stancel
Keyword(s):  
Electron Microscopic Examination ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Whole Cells ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Uterine Growth ◽  
Streptozotocin Induced Diabetes

Estradiol (E2)-stimulated uterine growth has been well characterized both biochemically and morphologically. Recent studies have shown that insulin plays an important role in the regulation of cellular development. This study examines the effect of streptozotocin-induced diabetes on E2-stimulated changes in the ultrastructure of the endometrium of the rat uterus.Sprague-Dawley rats were ovariectomized at 21 days of age. Diabetes, defined as blood glucose levels greater than 300mg%, was induced in half of these animals by the injection of 85mg streptozotocin/kg body weight.The remaining animals were classified as normal. Animals from both groups were injected with either 0.9% saline or 4μg E2/100gm body weight. At 18, 24, 36 and 48 hours post-injection of E2, uterine segments were collected from 8-10 animals in each experimental group and processed for electron microscopic examination. Uterine segments from saline-injected animals served as controls. Data summarized describe observations made from thin-sections and have not been extrapolated for whole cells.

The abdominal skin of female Sprague-Dawley rats is more sensitive than the back skin to drug-induced phototoxicity

2017 ◽  
Vol 88 ◽  
pp. 46-55 ◽  
Author(s):  
Kazuhiro Kuga ◽  
Hironobu Yasuno ◽  
Yumi Sakai ◽  
Yumiko Harada ◽  
Fumi Shimizu ◽  
...  
Keyword(s):  
Sprague Dawley ◽  
Drug Induced ◽  
Abdominal Skin ◽  
Sprague Dawley Rats

scholarly journals Neuroprotective Effects of Early Hypothermia Induced by Phenothiazines and DHC in Ischemic Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun Han ◽  
Xiao-kun Geng ◽  
Hangil Lee ◽  
Fengwu Li ◽  
Yuchuan Ding
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Glucose Transporter ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Ros Production ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Neuroprotective Effects ◽  
Sprague Dawley Rats

Background and Purpose. Studies have shown that interischemia hypothermia is able to reduce the size of myocardial infarctions and improve their clinical outcomes. The present study determined whether interischemia hypothermia induced by the pharmacological approach induced stronger neuroprotection in ischemic brains. Methods. Adult male Sprague Dawley rats were studied in 4 groups: (1) sham; (2) stroke; (3) stroke treated with pharmacological hypothermia before reperfusion (interischemia hypothermia); and (4) stroke treated with pharmacological hypothermia after reperfusion is initiated (inter-reperfusion hypothermia). The combination of chlorpromazine and promethazine with dihydrocapsaicin (DHC) was used to induce hypothermia. To compare the neuroprotective effects of drug-induced hypothermia between the interischemia and inter-reperfusion groups, brain damage was evaluated using infarct volume and neurological deficits at 24 h reperfusion. In addition, mRNA expressions of NADPH oxidase (NOX) subunits (gp91phox, p67phox, p47phox, and p22phox) and glucose transporter subtypes (GLUT1 and GLUT3) were determined by real-time PCR at 6 and 24 h reperfusion. ROS production was measured by flow cytometry assay at the same time points. Results. In both hypothermia groups, the cerebral infarct volumes and neurological deficits were reduced in the ischemic rats. At 6 and 24 h reperfusion, ROS production and the expressions of NOX subunits and glucose transporter subtypes were also significantly reduced in both hypothermia groups as compared to the ischemic group. While there were no statistically significant differences between the two hypothermia groups at 6 h reperfusion, brain damage was significantly further decreased by interischemia hypothermia at 24 h. Conclusion. Both interischemia and inter-reperfusion pharmacological hypothermia treatments play a role in neuroprotection after stroke. Interischemia hypothermia treatment may be better able to induce stronger neuroprotection after ischemic stroke. This study provides a new avenue and reference for stronger neuroprotective hypothermia before vascular recanalization in stroke patients.

scholarly journals Rats remember: Lack of drug-induced post-retrieval amnesia for auditory fear memories

2020 ◽  
Author(s):  
Laura Luyten ◽  
Anna Elisabeth Schnell ◽  
Natalie Schroyens ◽  
Tom Beckers
Keyword(s):  
Fear Conditioning ◽  
Critical Time ◽  
Fear Memory ◽  
Time Frame ◽  
List Type ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Pharmacological Agents ◽  
Administration Routes ◽  
Sprague Dawley Rats

AbstractWhen retrieved under specific circumstances, consolidated fear memories are thought to return to a labile state, thereby opening a window for modification (e.g., attenuation) of the memory. Several interventions during a critical time frame after this destabilization seem to be able to alter the retrieved memory, for example through pharmacological interference with the restabilization process, either by direct protein synthesis inhibition or indirectly, using drugs that can be safely administered in patients (e.g., propranolol).In a series of well-powered auditory fear conditioning experiments (four with propranolol, 10 mg/kg, two with rapamycin, 20-40 mg/kg, one with anisomycin, 150 mg/kg and cycloheximide, 1.5 mg/kg), we found no evidence for reduced cued fear memory expression during a drug-free test in adult male Sprague-Dawley rats that had previously received a systemic drug injection upon retrieval of the tone fear memory. All experiments used standard fear conditioning and reactivation procedures with freezing as the behavioral read-out (conceptual or exact replications of published reports) and common pharmacological agents. Additional tests confirmed that the applied drug doses and administration routes were effective in inducing their conventional effects on expression of fear (propranolol, acutely), body weight (rapamycin, anisomycin, cycloheximide) and consolidation of extinction memories (cycloheximide).Thus, in contrast with most published studies, we did not find evidence for drug-induced post-retrieval amnesia, underlining that this effect, as well as its clinical applicability, may be considerably more constrained and less readily reproduced than what the current literature would suggest.HighlightsWe aimed to replicate post-retrieval amnesia for auditory fear memories in ratsWe performed a series of well-powered pharmacological interference experimentsPropranolol, rapamycin, anisomycin or cycloheximide was injected upon retrievalBayesian stats found substantial evidence for the absence of post-retrieval amnesiaThe effect is less reproducible and generalizable than what the literature suggests

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