Induction of hepatic portal fibrosis, mitochondria damage, and extracellular vesicle formation in Sprague-Dawley rats exposed to copper, manganese, and mercury, alone and in combination

2020 ◽  
Vol 44 (2) ◽  
pp. 182-192 ◽  
Author(s):  
Priyanka Dhanraj ◽  
Chantelle Venter ◽  
Megan Jean Bester ◽  
Hester Magdalena Oberholzer
1999 ◽  
Vol 96 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Claire CONNOLLY ◽  
Teresa CAWLEY ◽  
P. Aiden MCCORMICK ◽  
James R. DOCHERTY

We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague–Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71±0.12 ;g) and noradrenaline (1.00±0.17 ;g) but not phenylephrine (0.86±0.10 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45±0.04 ;g, 0.57±0.07 ;g, 0.71±0.05 ;g respectively). In aortas from Sprague–Dawley rats, the maximum response to KCl (1.21±0.21 ;g) and phenylephrine (1.54±0.30 ;g) but not noradrenaline (0.93±0.09 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59±0.09 ;g, 0.76±0.11 ;g, 1.04±0.10 ;g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [3H]prazosin to α1-adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague–Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.


1991 ◽  
Vol 261 (1) ◽  
pp. R162-R165 ◽  
Author(s):  
J. Le Sauter ◽  
U. Noh ◽  
N. Geary

Specific antibodies to pancreatic glucagon in a dose sufficient to neutralize 1.5 ng glucagon in vitro were intraportally infused during the first 2 min of spontaneous meals in ad libitum-fed male Sprague-Dawley rats. In separate tests, glucagon antibodies stimulated feeding during the first spontaneous meal of the dark phase (73% mean increase in meal size) and during spontaneous meals in the last quarter of the dark phase (58% increase). These results indicate that a glucagon-sensitive satiety mechanism has a physiological role in the control of nocturnal feeding in rats.


1991 ◽  
Vol 261 (1) ◽  
pp. R154-R161 ◽  
Author(s):  
J. Le Sauter ◽  
N. Geary

We describe the first tests of intraportal pancreatic glucagon infusions during spontaneous meals in undisturbed, ad libitum-fed male Sprague-Dawley rats. Two-minute infusions beginning at meal onset and delivering 14 micrograms glucagon reduced the size and duration of both early and late nocturnal meals. After glucagon infusion during early nocturnal meals, neither the latency nor the size of the next meal was affected. Meal onset infusion of 3.4-14 micrograms glucagon/meal dose-dependently reduced late nocturnal meal size 19-64%. Full-meal glucagon infusions did not inhibit feeding more than 2-min infusions begun at meal onset or meal middle, despite fivefold differences in amount infused. These data indicate that spontaneous feeding is pharmacologically inhibited by prandial changes in hepatic portal glucagon concentration.


2021 ◽  
Vol 43 (3) ◽  
pp. 1997-2010
Author(s):  
Christian Bleilevens ◽  
Christian Beckers ◽  
Alexander Theissen ◽  
Tamara Fechter ◽  
Eva Miriam Buhl ◽  
...  

Background: Anesthetic-induced preconditioning (AIP) with volatile anesthetics is a well-known experimental technique to protect tissues from ischemic injury or oxidative stress. Additionally, plasmatic extracellular vesicle (EV) populations and their cargo are known to be affected by AIP in vitro, and to provide organ protective properties via their cargo. We investigated whether AIP would affect the generation of EVs in an in vivo rat model. Methods: Twenty male Sprague Dawley rats received a repetitive treatment with either isoflurane or with sevoflurane for a duration of 4 or 8 weeks. EVs from blood plasma were characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM) and Western blot. A scratch assay (H9C2 cardiomyoblast cell line) was performed to investigate the protective capabilities of the isolated EVs. Results: TEM images as well as Western blot analysis indicated that EVs were successfully isolated. The AIP changed the flotillin and CD63 expression on the EV surface, but not the EV concentration. The scratch assay did not show increased cell migration and/or proliferation after EV treatment. Conclusion: AIP in rats changed the cargo of EVs but had no effect on EV concentration or cell migration/proliferation. Future studies are needed to investigate the cargo on a miRNA level and to investigate the properties of these EVs in additional functional experiments.


1997 ◽  
Vol 13 (1) ◽  
pp. 81-89
Author(s):  
K.M. Lee ◽  
S. Muralidhara ◽  
C.E. Dallas ◽  
J.V. Bruckner

It is possible that a substantial portion of orally administered volatile organic chemicals (VOCs) may volatilize within the warm environment of the gastrointestinal (GI) tract and escape via the esophagus before being absorbed. The objective of this study was to test this hypothesis with a representative VOC., 1,1,2-trichloroethylene (TCE). Upon hepatic portal vein (PV) injection, complete systemic absorption of TCE was assumed. Thus, exhaled TCE after PV injection should originate only from pulmonary exhalation. In contrast, TCE volatilized in the gut may also contribute to the amounts of TCE exhaled by orally (PO) dosed animals. Male Sprague-Dawley rats (320–380g) were given 8 or 16 mg TCE/kg bw in an aqueous Alkamuls® emulsion (RhonePoulenc, Cranbury, New Jersey). For the PO groups both doses were given by gavage, and for the PV groups the lower dose was injected into the PV as a bolus and the higher dose given as a 20 mm infusion. Serial blood samples were taken from an indwelling carotid arterial cannula and analyzed for their TCE content by headspace gas chromatography (GC), so that the areas-under-blood-concentration-versus-time curves (AUCs) could be determined. Serial exhaled air samples were collected from a sampling port in a miniaturized one-way breathing valve and TCE measured by GC analysis to delineate exhaled breath concentration-versus-time-curves (EAUCs). Exhaled breath levels of TCE paralleled blood levels of TCE throughout the monitoring periods. Evidence against the aforementioned hypothesis was provided by comparison of ratios of blood AUCs and exhaled breath EAUCs: values for ratios of AUCpo/AUCpv and EAUCpo/EAUCpv were the same, as were EAUC/AUC ratios for the PO and PV groups. The EAUCs in the PO groups should have been higher, had there been substantial extrusion of volatilized TCE from the GI tract.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1236-1236
Author(s):  
Andrew Thaw

Abstract Objectives To examine the release of satiety-inducing cytokines in response to diets rich in fat, carbohydrates or protein. Methods The feeding behavior of 40 male Sprague-Dawley rats was continuously monitored for 23 hours per day. Food was made available at 1200 each day and removed at 1800 each day. Rats were divided into 4 groups of 10 rats each and each group received a specific diet (60% fat, 60% carbohydrate, 60% protein, or normal rat chow) for 14 days. On the 15th day, rats were presented with their meal and allowed one hour to eat. Next, rats were removed from their chamber, administered an anesthetic dose of Chloral Hydrate, and had blood (hepatic portal vein) and tissue (small intestine) removed and saved for analysis before being euthanized. Samples were later tested for the presence of cytokines using standard ELIZAs. 2 rats from each group were not allowed to eat on the day of testing and their blood an tissue samples were used as a baseline. Results Results show a clear release of cytokines (IL-IB and TNF-a…but not IL-6) in both the blood and tissue samples collected. Tissue showed the highest release of IL-1B in response to the balanced diet (1050 pg/ml) with the other diets each releasing between 340–550 pg/ml. The baseline (no food) group of rats had IL-1B levels of 155 pg/ml. TNFa had a similar but lower release profile, while IL-6 was negligible. Conclusions The release of immune factors in response to diet is supported and may provide novel interventions with respect to satiety. It does not appear that the specific content of the diet is as critical as a balanced diet with respect to cytokine release. Fat, surprisingly, had a limited effect on the release of cytokines. It may be that fat requires more time to express its effects on the immune cells; or it may that fat based satiety uses mechanisms other than immune factors to enhance satiety. Overall, our findings point to a role for immune factors in the regulation of hunger and satiety that has only been minimally examined thus far. Continued work in this area is warranted to determine the effects of the immune system in normal eating behavior as well as disordered eating. Funding Sources This research was supported by the Millsaps College Faculty Development Grant and the Millsaps College Honors Project.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

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.


Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser

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.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

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.


Author(s):  
Russell N. A. Cecil ◽  
H. Clarke Anderson

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.


Sign in / Sign up

Export Citation Format

Share Document