Acute Inhibition of Lymphatic Cholesterol Transport in Rat Intestine by SCH 58053

Hayashi, Hiroshi; Kanai, Setsuko; Yamada, Yoshihiko; Tsushima, Motoo; Miyasaka, Kyoko

doi:10.5551/jat.13.240

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…Sprague-Dawley rats develop hyperlipidemia by triton administration [326]. Lymphatic cholesterol transport system [327] and the rate of hepatic secretion of VLDL in triton-induced hyperlipidemic rat [328] has been explored. Corpulent rats strain developed by cross between Sprague-Dawley rats and spontaneously hypertensive rats (SHR) are hypertensive, obese, hyperlipidemic and hyperinsulinemic [22,329,330].…”

Section: Ratmentioning

confidence: 99%

“…Ezetimibe, an inhibitor of intestinal cholesterol absorption, acts at the brush border of the small intestine and inhibits the uptake of dietary and biliary cholesterol into the enterocytes [494,495]. Caco2 cells an intestinal cell line used in several studies to explore mechanistic aspect of dietary and biliary cholesterol uptake has been used to assess the efficacy of various inhibitors such as ezetimibe [494], SCH5803 [327], SC-435 (ASBT inhibitor) [463]. The effect of test compounds on lipoprotein production in Caco2 human intestinal cells can be evaluated by incubating for 24h with test agent or 10 mol/L of atorvastatin.…”

Section: Enterocytesmentioning

confidence: 99%

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Models to Study Atherosclerosis: A Mechanistic Insight

Singh

Tiwari

Dikshit

et al. 2009

CVP

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The recent failure of candidate drugs like cholesterol ester transfer protein (CETP) and acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors calls for a revised approach for screening anti-atherosclerotic drugs and development of new models of atherosclerosis. For this it is important to understand the mechanism of the disease in a particular model. Models simultaneously showing hyperlipidemia, inflammation and associated complications of diabetes and hypertension will serve the purpose better as they mimic the actual clinical condition. Besides this, analyzing candidate molecules in vivo, in vitro and at various levels of atherosclerosis progression is important. Models based on various cells and process involved in atherosclerosis should be used for screening candidate molecules. The challenge lies in bridging the gap between genetically friendly small animal and human-like bigger animal models. Sequencing of the mouse and human genome, development of a single nucleotide polymorphism (SNP) database and in silico quantitative trait loci (QTL) linkage analysis may enhance the understanding of atherosclerosis and help develop new therapeutic targets.

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Section: Ratmentioning

confidence: 99%

Section: Enterocytesmentioning

confidence: 99%

Models to Study Atherosclerosis: A Mechanistic Insight

Singh

Tiwari

Dikshit

et al. 2009

CVP

View full text Add to dashboard Cite

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“…In particular, abdominal obesity is associated with increased cardiovascular risk factors, elevated blood pressure, increased triglycerides, fasting glucose, and decreased high-density lipoprotein cho-blockade may be potentially beneficial against atherosclerosis 5) . The reverse cholesterol transport (RCT) is one of the major protective systems against atherosclerosis 6,7) . Recently, ATP-binding cassette (ABC) transporter G1 was found to induce an alternative cholesterol efflux pathway from macrophages and prevent cellular lipid accumulation 8,9) .…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid 1 Receptor Blockade Reduces Atherosclerosis with Enhances Reverse Cholesterol Transport

Sugamura

Sugiyama

Fujiwara

et al. 2010

JAT

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Aim: A recent clinical study using coronary intravascular ultrasound showed that rimonabant, a cannabinoid 1 (CB1) receptor antagonist, significantly reduced total atheroma volume, suggesting that CB1 receptor blockade could be beneficial in anti-atherogenic therapy. The reverse cholesterol transport (RCT) system plays important roles in atherogenesis. We investigated whether CB1 receptor blockade could modulate atherogenesis in mice. Methods and Results: Oral administration of rimonabant (8 mg/kg/day) to apolipoprotein E-deficient mice for 3 months significantly reduced the relative area of atherosclerotic lesions in the aorta (vehicle; 12.6 4.0% vs. rimonabant; 9.7 2.3, n 12 each, p 0.05) with an increase in serum adiponectin levels (15.6 2.3 g/mL vs. 12.2 2.1, n 12 each, p 0.001), without affecting body weight or serum cholesterol levels. Rimonabant tended to increase serum high-density lipoprotein cholesterol (HDL-C) (p 0.05). The relative area of atherosclerotic lesions in the aorta correlated inversely with serum HDL-C levels (r 0.45, n 24, p 0.05). Rimonabant upregulated the mRNA expression levels of various components of the RCT system on THP-1 cell-derived macrophages (scavenger receptor B1: 1.15 0.12 fold, n 6; p 0.05, ATP-binding cassette [ABC] transporter G1: 1.23 0.11 fold, n 6; p 0.01), but not ABCA1 (1.13 0.20 fold, n 6; p 0.13). Conclusion: CB1 receptor blockade reduced atherosclerosis in apoE-deficient mice through an increase in serum adiponectin levels and activation of the RCT system. CB1 receptor blockade may be therapeutically beneficial for atherogenesis by increasing the serum adiponectin level and enhancing of the RCT system.

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Experimental research Influence of ezetimibe on selected parameters of oxidative stress in rat liver subjected to ischemia/reperfusion

Trocha¹,

Merwid-Ląd²,

Chlebda³

et al. 2014

aoms

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IntroductionIschemia/reperfusion (I/R) is considered to be one of the main causes of liver damage after transplantation. The authors evaluated the effect of ezetimibe on selected oxidative stress parameters in ischemic/reperfused (I/R) rat liver.Material and methodsRats were administered ezetimibe (5 mg/kg) (groups E and E-I/R) or saline solution (groups C and C-I/R) intragastrically for 21 days. Livers of animals in groups C-I/R and E-I/R were subjected to 60 min of partial ischemia (left lateral and median lobes) followed by 4 h of reperfusion. Alanine and asparagine aminotransferase (ALT, AST) activity was determined in blood before I/R and during reperfusion (at 15 and 240 min). After the reperfusion period, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx) were determined in liver homogenates using colorimetric methods.ResultsEzetimibe caused a significant increase in GSH level in groups subjected to I/R (E-I/R (99.91 ±9.01) vs. C-I/R (90.51 ±8.87), p < 0.05). Additionally, under I/R the decrease of GPx activity in the drug-treated group was lower compared to the non-treated group (E-I/R (3.88 ±1.11) vs. E (5.31 ±1.83), p = 0.076). Neither ezetimibe nor I/R affected SOD or MDA levels. I/R produced a significant increase in aminotransferase levels (ALT240-0: C-I/R (42.23 ±43.56) vs. C (9.75 ±11.09), and E-I/R (39.85 ±26.53) vs. E (4.38 ±1.36), p < 0.05 in both cases; AST 240-0: E-I/R (53.87 ±17.23) vs. E (24.10 ±9.66), p < 0.05) but no effect of ezetimibe on those enzymes was found.ConclusionsEzetimibe demonstrates antioxidant properties in rat livers subjected to I/R. However, neither a hepatoprotective nor a hepatotoxic effect of ezetimibe was demonstrated, regardless of I/R.

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Acute Inhibition of Lymphatic Cholesterol Transport in Rat Intestine by SCH 58053

Cited by 3 publications

References 26 publications

Models to Study Atherosclerosis: A Mechanistic Insight

Models to Study Atherosclerosis: A Mechanistic Insight

Cannabinoid 1 Receptor Blockade Reduces Atherosclerosis with Enhances Reverse Cholesterol Transport

Experimental research Influence of ezetimibe on selected parameters of oxidative stress in rat liver subjected to ischemia/reperfusion

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