Chronic Cadmium Exposure Alters Cardiac Matrix Metalloproteinases in the Heart of Sprague-Dawley Rat

The aim of this study was to evaluate the role of chronic cadmium exposure in modulating cardiac matrix metalloproteinases (MMPs) in the heart of rats. Adult male Sprague-Dawley rats were exposed to 15 ppm CdCl2 in drinking water for 10 weeks followed by withdrawal of cadmium treatment for 4 weeks. Following the completion of the treatment, gene expression of inflammatory mediators (IL-1β, IL-6, IL-10, TNF-α and NF-κB), protein expression of MMP-2, MMP-9 and their respective inhibitors- TIMP-1 and TIMP-2, and gelatinolytic activity of MMP-2 and MMP-9 were determined. At the protein level, cadmium incites a differential effect on the expression and activity of gelatinases and their endogenous inhibitors in an exposure-dependent manner. Results also show that the administered cadmium dose elicits an inflammatory response until week 10 that slightly diminishes after 4 weeks. This study provides evidence of cadmium-induced imbalance in the MMP-TIMP system in the cardiac tissue. This imbalance may be mediated by cadmium-induced inflammation that could contribute to various cardiovascular pathologies.

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

Current Bioactive Compounds ◽

10.2174/1573407217666210816105252 ◽

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.

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Dehydroepiandrosterone prevents dexamethasone-induced hypertension in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.2.e210 ◽

1992 ◽

Vol 263 (2) ◽

pp. E210-E213 ◽

Cited By ~ 1

Author(s):

Y. Shafagoj ◽

J. Opoku ◽

D. Qureshi ◽

W. Regelson ◽

M. Kalimi

Keyword(s):

Weight Loss ◽

Genetic Model ◽

Experimental Hypertension ◽

Dependent Manner ◽

Sprague Dawley ◽

Spontaneously Hypertensive ◽

Sprague Dawley Rats ◽

Induced Hypertension ◽

Dose Dependent

Dehydroepiandrosterone (DHEA) is an endogenous steroid having a wide variety of biological and biochemical effects. In the present study, we have examined the role of DHEA on various rodent models of experimental hypertension. Sprague-Dawley rats were given subcutaneous injections of 1.5 mg dexamethasone every alternate day, resulting in an increase in systolic blood pressure within 1 wk. Interestingly, administration of a pharmacological dose of 1.5, 3, or 7.5 mg DHEA along with dexamethasone prevented dexamethasone-induced hypertension in a dose-dependent manner. DHEA had no effect on the hypertension induced by deoxycorticosterone acetate (DOCA)-salt administration using uninephrectomized rats or on the genetic model of spontaneously hypertensive rats. Dexamethasone administration resulted in a significant weight loss in rats, which was not prevented by simultaneous administration of DHEA. These results indicate that dexamethasone-mediated weight loss may involve mechanisms separate from its hypertensive action. Dexamethasone treatment resulted in a significant decrease in food consumption that was not reversed by DHEA. It is concluded that DHEA at doses above physiological levels when given subcutaneously has no effect on DOCA-salt or a genetic model of hypertension but has a beneficial effect on dexamethasone-induced hypertension.

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Role of cytochrome P-450 in endogenous antipyresis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.2.r455 ◽

2000 ◽

Vol 279 (2) ◽

pp. R455-R460 ◽

Cited By ~ 33

Author(s):

Wieslaw Kozak ◽

Matthew J. Kluger ◽

Anna Kozak ◽

Maciej Wachulec ◽

Karol Dokladny

Keyword(s):

Arachidonic Acid ◽

Intraperitoneal Administration ◽

Dependent Manner ◽

Epoxyeicosatrienoic Acid ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Rats And Mice ◽

Dose Dependent ◽

Cytochrome P 450

In previous reports, we (15, 18) and others (29) demonstrated data showing that various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis. The aim of this study was to further test the hypothesis that the P-450-dependent epoxygenase pathway of arachidonic acid is part of the homeostatic system to control the height of fever. Sprague-Dawley rats were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide (LPS; 80 μg/kg). We demonstrate that intraperitoneal administration of P-450 inducers (bezafibrate and dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a dose-dependent manner. In complementary experiments, rats were implanted with brain cannulas in addition to the biotelemeters. Various isomers of epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to 10 μg/rat to test their influence on LPS-induced fever in rats. Four of five isomers were antipyretic in a dose-dependent manner. The most potent antipyretic isomers were 11,12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9-EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part of the endogenous antipyretic system.

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Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2023899118 ◽

2021 ◽

Vol 118 (11) ◽

pp. e2023899118

Author(s):

Takeshi Masaki ◽

Makoto Okazawa ◽

Ryotaro Asano ◽

Tadakatsu Inagaki ◽

Tomohiko Ishibashi ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Aryl Hydrocarbon Receptor ◽

Vascular Lesions ◽

Dependent Manner ◽

Sprague Dawley ◽

Aryl Hydrocarbon ◽

Sprague Dawley Rats ◽

Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown. Here, we explore the role of AHR in the pathogenesis of PAH. AHR agonistic activity in serum was significantly higher in PAH patients than in healthy volunteers and was associated with poor prognosis of PAH. Sprague–Dawley rats treated with the potent endogenous AHR agonist, 6-formylindolo[3,2-b]carbazole, in combination with hypoxia develop severe pulmonary hypertension (PH) with plexiform-like lesions, whereas Sprague–Dawley rats treated with the potent vascular endothelial growth factor receptor 2 inhibitors did not. Ahr-knockout (Ahr−/−) rats generated using the CRISPR/Cas9 system did not develop PH in the SU5416/hypoxia model. A diet containing Qing-Dai, a Chinese herbal drug, in combination with hypoxia led to development of PH in Ahr+/+ rats, but not in Ahr−/− rats. RNA-seq analysis, chromatin immunoprecipitation (ChIP)-seq analysis, immunohistochemical analysis, and bone marrow transplantation experiments show that activation of several inflammatory signaling pathways was up-regulated in endothelial cells and peripheral blood mononuclear cells, which led to infiltration of CD4+ IL-21+ T cells and MRC1+ macrophages into vascular lesions in an AHR-dependent manner. Taken together, AHR plays crucial roles in the development and progression of PAH, and the AHR-signaling pathway represents a promising therapeutic target for PAH.

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Influence of Slice Thickness and Culture Conditions on the Metabolism of 7-Ethoxycoumarin in Precision-cut Rat Liver Slices

Alternatives to Laboratory Animals ◽

10.1177/026119299802600417 ◽

1998 ◽

Vol 26 (4) ◽

pp. 541-548

Author(s):

Roger J. Price ◽

Anthony B. Renwick ◽

Paula T. Barton ◽

J. Brian Houston ◽

Brian G. Lake

Keyword(s):

Gas Phase ◽

Rat Liver ◽

Xenobiotic Metabolism ◽

Culture Conditions ◽

Slice Thickness ◽

Dependent Manner ◽

Sprague Dawley ◽

Liver Slices ◽

Sprague Dawley Rats ◽

Rat Livers

This study investigated the effects of some experimental variables on the rate of xenobiotic metabolism in precision-cut rat liver slices. Liver slices of 123 ± 8μm (mean ± SEM of six slices), 165 ± 3μm, 238 ± 6μm and 515 ± 14μm thickness were prepared from male Sprague-Dawley rats, and incubated in RPMI 1640 medium in an atmosphere of 95% O2/5% CO2 by using a dynamic organ culture system. Liver slices of all thicknesses metabolised 10μM 7-ethoxycoumarin to total (free and conjugated) 7-hydroxycoumarin in a time-dependent manner. The rate of 7-ethoxycoumarin metabolism was greatest in 165μm thick slices and slowest in 515μm thick slices, being 2.74 ± 0.19pmol/minute/mg slice protein and 0.69 ± 0.07pmol/minute/mg slice protein, respectively. No marked effects on the rate of 7-ethoxycoumarin metabolism in liver slices were observed either by changing the medium to Earle's balanced salt solution (EBSS) or by changing the gas phase to 95% air/5% CO2. Moreover, the perfusion of rat livers with EBSS at 2–4°C, prior to preparation of tissue cores, did not enhance 7-ethoxycoumarin metabolism in rat liver slices. In this study, the optimal slice thickness was 175μm, with higher rates of 7-ethoxycoumarin metabolism being observed than with 250μm thick slices, which are often used for studies of xenobiotic metabolism. Variable results were obtained with slices of around 100–120μm thickness, which may be attributable to the ratio between intact hepatocytes and cells damaged by the slicing procedure in these very thin slices.

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Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00972.2010 ◽

2011 ◽

Vol 300 (5) ◽

pp. H1781-H1787 ◽

Cited By ~ 25

Author(s):

Sachin S. Kandlikar ◽

Gregory D. Fink

Keyword(s):

Control Period ◽

Whole Body ◽

Renal Nerves ◽

Experimental Hypertension ◽

Sympathetic Activation ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Salt Hypertension ◽

Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

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Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.2.h751 ◽

1994 ◽

Vol 267 (2) ◽

pp. H751-H756 ◽

Cited By ~ 7

Author(s):

A. W. Cowley ◽

E. Szczepanska-Sadowska ◽

K. Stepniakowski ◽

D. Mattson

Keyword(s):

Body Weight ◽

Arginine Vasopressin ◽

Plasma Catecholamines ◽

Plasma Osmolality ◽

Sprague Dawley ◽

Prolonged Administration ◽

Chronic Stimulation ◽

Sustained Hypertension ◽

Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

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Dietary conjugated linoleic acid (CLA) induces apoptosis of colonic mucosa in 1,2-dimethylhydrazine-treated rats: a possible mechanism of the anticarcinogenic effect by CLA

British Journal Of Nutrition ◽

10.1079/bjn2001445 ◽

2001 ◽

Vol 86 (5) ◽

pp. 549-555 ◽

Cited By ~ 77

Author(s):

Hyun S. Park ◽

Ji H. Ryu ◽

Yeong L. Ha ◽

Jung H. Y. Park

Keyword(s):

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Control Diet ◽

Terminal Deoxynucleotidyl Transferase ◽

Prostaglandin E ◽

Dependent Manner ◽

Sprague Dawley ◽

Tumour Incidence ◽

Sprague Dawley Rats ◽

Dietary Conjugated Linoleic Acid

One of the objectives of the present study was to investigate whether 1 % conjugated linoleic acid (CLA) in the diet reduced tumour incidence in the colon of 1,2-dimethylhydrazine (DMH)-treated rats. Colon cancer was induced by injecting 6-week-old, male, Sprague–Dawley rats with 15 mg/kg DMH twice per week for 6 weeks. They were fed either 1 % CLA or a control diet ad libitum for 30 weeks. Dietary CLA significantly decreased colon tumour incidence (P<0·05). Our second objective was to investigate whether apoptosis in the colon mucosa of DMH-treated rats was affected by the amount of dietary CLA and whether the changes in apoptosis were related to those in fatty acid-responsive biomarkers. For this purpose, rats were killed after being fed a diet containing 0 %, 0·5 %, 1 % or 1·5 % CLA for 14 weeks. CLA was undetected in the mucosa of rats fed the 0 % CLA diet and increased to 5·9 mg/g phospholipid in rats fed the 0·5 % diet. The apoptotic index estimated by the terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling technique was increased by 251 % and the 1,2-diacylglycerol content was decreased by 57 % in rats fed 0·5 % CLA. No further changes in these variables were observed when CLA in the diet was raised to 1·0 % or 1·5 %. However, dietary CLA decreased mucosal levels of prostaglandin E2, thromboxane B2 and arachidonic acid in a dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanisms probably involving increased apoptosis.

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Effects of Blood Glucose Changes and Physostigmine on Anesthetic Requirements of Halothane in Rats

Anesthesiology ◽

10.1097/00000542-199708000-00023 ◽

1997 ◽

Vol 87 (2) ◽

pp. 354-360 ◽

Cited By ~ 1

Author(s):

Yumiko Ishizawa ◽

Shuichiro Ohta ◽

Hiroyuki Shimonaka ◽

Shuji Dohi

Keyword(s):

Blood Glucose ◽

Blood Glucose Level ◽

Glucose Level ◽

Minimum Alveolar Concentration ◽

Severe Hypoglycemia ◽

Dependent Manner ◽

Sprague Dawley ◽

Control Value ◽

Sprague Dawley Rats ◽

Brain Acetylcholine

Background Although hyper- and hypoglycemia induce neurophysiologic changes, there have been no reports on the effects of blood glucose changes on anesthetic requirements. This study examined the effects of hyper- and hypoglycemia on the minimum alveolar concentration (MAC) of halothane in rats. In addition, based on a previous finding that the level of brain acetylcholine was reduced during mild hypoglycemia, the authors examined the influence of physostigmine on MAC during hypoglycemia. Methods In Sprague-Dawley rats, anesthesia was induced and maintained with halothane in oxygen and air. The MAC was determined by observing the response to tail clamping and tested during mild hypoglycemia (blood glucose level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl) induced by insulin and glucose infusion, respectively (experiment 1). The effects of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl; experiment 2). Results In experiment 1, mild hypoglycemia significantly reduced the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/- 0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg reduced MAC. Conclusions Hypoglycemia reduced anesthetic requirements in a degree-dependent manner, whereas hyperglycemia had no effects. Although the mechanism of hypoglycemic MAC reduction needs further investigations, physostigmine studies suggest that this may not be related to inhibition of cholinergic transmission.

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Methomyl induced effect on fortilin and S100A1 in serum and cardiac tissue: Potential biomarkers of toxicity

Human & Experimental Toxicology ◽

10.1177/0960327118814153 ◽

2018 ◽

Vol 38 (3) ◽

pp. 371-377

Author(s):

SD Nusair ◽

AN Joukhan ◽

AH Bani Rashaid ◽

AM Rababa’h

Keyword(s):

Toxic Effect ◽

Cardiac Tissue ◽

Cardiac Fibroblasts ◽

Study Group ◽

Sprague Dawley ◽

Cardiac Tissues ◽

Sprague Dawley Rats ◽

Cervical Dislocation ◽

Potential Biomarkers

Methomyl toxicity has been reported as a cause of several accidental and suicidal fatalities. The study is evaluating the effect of lethal methomyl toxicity on fortilin and S100A1 in serum and cardiac tissues. Adult 96 female Sprague-Dawley rats were divided equally into a control (euthanized by cervical dislocation) and a study group (overdosed with methomyl). The levels of fortilin and S100A1 in serum were measured antemortem (to establish the basal levels in serum) and postmortem (to evaluate changes after methomyl exposure) using enzyme-linked immunoassay. S100A1 was immunostained in sections from cardiac tissues. Both proteins in the control were not significantly different ( p > 0.05) compared with the antemortem levels. On the contrast, both biomarkers levels in the intoxicated group were remarkably higher ( p < 0.001) than the control and the antemortem levels. Ventricular tissues from the intoxicated rats presented depleted S100A1 immunostain in cardiomyocytes localized mainly in the epicardium with deeply stained adjacent cardiac fibroblasts. The cardiomyocytes were damaged with a prominent loss of striations compared to normal cardiac tissues from the control. The present outcomes explain to a certain degree the potential toxic effect of methomyl poisoning on the cardiac tissue. Both proteins could be added to the currently available battery of markers for assessing methomyl toxicity.

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