Role of endotoxin in the hypermetabolic state  after acute ethanol exposure

This study investigated the role of endotoxin in the hypermetabolic state or swift increase in alcohol metabolism (SIAM) due to acute ethanol exposure. Female Sprague-Dawley rats (100–120 g) were given ethanol (5 g/kg) by gavage. Endotoxin measured in plasma from portal blood was not detectable in saline-treated controls; however, 90 min after ethanol, endotoxin was increased to 85 ± 14 pg/ml, and endotoxin clearance was diminished by ∼50%. Oxygen uptake in perfused livers was increased 48% by ethanol, and production of PGE2 by isolated Kupffer cells was increased similarly. These effects were blunted by elimination of gram-negative bacteria and endotoxin with antibiotics before ethanol administration. To reproduce ethanol-induced endotoxemia, endotoxin was infused via the mesenteric vein at a rate of 2 ng ⋅ kg−1 ⋅ h−1. Endotoxin mimicked the effect of ethanol on oxygen uptake. The specific Kupffer cell toxicant GdCl3completely prevented increases in oxygen uptake due to endotoxin. These findings demonstrate that endotoxin plays a pivotal role in SIAM, most likely by stimulating eicosanoid release from Kupffer cells.

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Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.6.g1076 ◽

2001 ◽

Vol 280 (6) ◽

pp. G1076-G1082 ◽

Cited By ~ 30

Author(s):

Peter Schemmer ◽

Nobuyuki Enomoto ◽

Blair U. Bradford ◽

Hartwig Bunzendahl ◽

James A. Raleigh ◽

...

Keyword(s):

Liver Transplantation ◽

Kupffer Cells ◽

Cell Function ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Hypermetabolic State ◽

Hypoxia Marker ◽

Factor Α ◽

Necrosis Factor

Harvesting trauma to the graft dramatically decreases survival after liver transplantation. Since activated Kupffer cells play a role in primary nonfunction, the purpose of this study was to test the hypothesis that organ manipulation activates Kupffer cells. To mimic what occurs with donor hepatectomy, livers from Sprague-Dawley rats underwent dissection with or without gentle organ manipulation in a standardized manner in situ. Perfused livers exhibited normal values for O2 uptake (105 ± 5 μmol · g−1 · h−1) measured polarigraphically; however, 2 h after organ manipulation, values increased significantly to 160 ± 8 μmol · g−1 · h−1 and binding of pimonidazole, a hypoxia marker, increased about threefold ( P < 0.05). Moreover, Kupffer cells from manipulated livers produced three- to fourfold more tumor necrosis factor-α and PGE2, whereas intracellular calcium concentration increased twofold after lipopolysaccharide compared with unmanipulated controls ( P < 0.05). Gadolinium chloride and glycine prevented both activation of Kupffer cells and effects of organ manipulation. Furthermore, indomethacin given 1 h before manipulation prevented the hypermetabolic state, hypoxia, depletion of glycogen, and release of PGE2 from Kupffer cells. These data indicate that gentle organ manipulation during surgery activates Kupffer cells, leading to metabolic changes dependent on PGE2 from Kupffer cells, which most likely impairs liver function. Thus modulation of Kupffer cell function before organ harvest could be beneficial in human liver transplantation and surgery.

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Highlight Article: Conditioning the neuroimmune response to ethanol using taste and environmental cues in adolescent and adult rats

Experimental Biology and Medicine ◽

10.1177/1535370219831709 ◽

2019 ◽

Vol 244 (5) ◽

pp. 362-371

Author(s):

Anny Gano ◽

Ricardo M Pautassi ◽

Tamara L Doremus-Fitzwater ◽

Thaddeus M Barney ◽

Andrew S Vore ◽

...

Keyword(s):

Young Adults ◽

Alcohol Abuse ◽

Drugs Of Abuse ◽

Ethanol Exposure ◽

Single Trial ◽

Sprague Dawley ◽

Adult Rats ◽

Acute Ethanol ◽

Conditioned Effects

Our work in adult Sprague-Dawley rats has shown elevation of the cytokine Interleukin (IL)-6 in the hippocampus and amygdala following acute and repeated binge-like doses of ethanol during intoxication. Previously, we have shown that in adults, the central IL-6 response to a sub-threshold dose of ethanol was sensitized by repeated pairings of ethanol as an unconditioned stimulus (US) with an odor conditioned stimulus (CS).In the present studies, acute ethanol exposure (4 g/kg intraperitoneal) was paired with a combined odor and taste cue using a single trial learning procedure, after which rats were tested for conditioned effects of the CS on neuroimmune gene expression. We found that IL-6 was significantly elevated in the amygdala based on exposure to the CS after just one CS–US pairing in young adolescent rats (age P32–40), an effect that was more modest in young adults (P72–80). These data indicate that, despite a normal disposition toward a blunted neuroimmune response to ethanol, adolescents were more sensitive than adults to forming learned associations between ethanol’s neuroimmune effects and conditioned stimuli. Given the emergent role of the immune system in alcoholism, such as regulating ethanol intake, these ethanol-induced conditioned effects on cytokine levels may contribute to our understanding of the unique attributes that make adolescence a time period of vulnerability in the development of later alcohol abuse behaviors. Impact statement A combined odor and taste cue was paired with a binge-like ethanol exposure (4 g/kg intraperitoneal) using a single-trial learning paradigm. Re-exposure to the CS alone was sufficient to evoke a conditioned Interleukin (IL)-6 elevation in the amygdala in adolescents, an effect that was not observed in young adults. This demonstrates a particular sensitivity of adolescents to alcohol-associated cues and neuroimmune learning, whereas prior work indicated that adults require multiple pairings of ethanol to the CS in order to achieve a conditioned amygdala IL-6 response. While the role of immune conditioning has been studied in other drugs of abuse, these findings highlight a previously unknown aspect of alcohol-related learning. Given the emergent importance of the neuroimmune system in alcohol abuse, these findings may be important for understanding cue-induced reinstatement of alcohol intake among problem drinkers.

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Effects of acute ethanol administration and chronic stress exposure on social investigation and 50kHz ultrasonic vocalizations in adolescent and adult male Sprague–Dawley rats

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2013.01.012 ◽

2013 ◽

Vol 105 ◽

pp. 17-25 ◽

Cited By ~ 5

Author(s):

Amanda R. Willey ◽

Linda P. Spear

Keyword(s):

Chronic Stress ◽

Adult Male ◽

Ultrasonic Vocalizations ◽

Ethanol Administration ◽

Stress Exposure ◽

Sprague Dawley ◽

Social Investigation ◽

Sprague Dawley Rats ◽

Acute Ethanol

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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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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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Transient Neonatal Cryptosporidium parvum Infection Triggers Long-Term Jejunal Hypersensitivity to Distension in Immunocompetent Rats

Infection and Immunity ◽

10.1128/iai.02055-05 ◽

2006 ◽

Vol 74 (7) ◽

pp. 4387-4389 ◽

Cited By ~ 15

Author(s):

Rachel Marion ◽

Asiya Baishanbo ◽

Gilles Gargala ◽

Arnaud François ◽

Philippe Ducrotté ◽

...

Keyword(s):

Cryptosporidium Parvum ◽

Myeloperoxidase Activity ◽

Sprague Dawley ◽

Depressor Response ◽

Sprague Dawley Rats

ABSTRACT In 5-day-old immunocompetent Sprague-Dawley rats infected with either 102 or 105 Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.

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Effects of Xiang Sha Yang Wei Wan on Ethanol-Induced Gastric Ulcer in Sprague Dawley Rats: a Histological Study

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v12i2.502 ◽

2020 ◽

Vol 12 (2) ◽

Author(s):

Al-Qaraghuli AMS ◽

Abdel Wahab EMN ◽

Al-Ani IM ◽

Faisal GG

Keyword(s):

Gastric Ulcer ◽

Oral Dose ◽

Histological Study ◽

Treated Group ◽

Ethanol Administration ◽

Gastric Mucosal Lesion ◽

Sprague Dawley ◽

Group I ◽

Sprague Dawley Rats ◽

Group Ii

Introduction: Xiang Sha Yang Wei Wan (XSYWW) is a Chinese traditional medicine that is used for gastrointestinal disorders, specifically gastric ulcer in many countries of South-East Asia. The aim of the study was to evaluate the potential effects of XSYWW on ethanol-induced gastric ulcer in rats by means of histological Study. On a similar basis of treatment, ranitidine, a conventional medication was used as gold standard. Methods: Fifty five male Sprague-Dawley rats (250-300 gm) were divided into four groups. Group I (ethanol treated group) was the control group and gastric ulcers were induced by administering 100% ethanol (1 ml/200 g). Group II (Pre-treatment group) was divided into two subgroups; they were orally fed with 1.0 gm/kg and 2.0 gm/kg respectively of XSYWW solution. Thirty minutes later they were administered with absolute ethanol as in group I. Group III, was given an oral dose of 2gm/kg of XSYWW solution after one hour of ethanol administration. Group IV was given an oral dose of 200mg/kg ranitidine solution after one hour of ethanol administration. Five rats from groups I, III and IV were sacrificed on day 1, 2 and 3 while the animals of group II were sacrificed one hour after ethanol administration. Results: Histological study of the stomachs from ethanol treated rats showed multiple ulcers of various depths that reached the muscularis and the serosa. Conclusion: Pre or post-treated rats with XSYWW showed that XSYWW has protective effect against ethanol-induced gastric mucosal lesion. However, there was a faster and more complete healing process in the ranitidine treated group when compared to the XSYWW treated subjects.

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