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Selected AbstractsChronic Ethanol Feeding Alters Hepatocyte Memory Which is not Altered by Acute FeedingALCOHOLISM, Issue 4 2009F. Bardag-Gorce Background:, Gene expression changes in the liver after acute binge drinking may differ from the changes seen in chronic ethanol feeding in the rat. The changes in gene expression after chronic ethanol feeding may sensitize the liver to alcohol-induced liver damage, which is not seen after acute binge drinking. Methods:, To test this hypothesis, gene microarray analysis was performed on the livers of rats (n = 3) fed an acute binge dose of ethanol (6 g/kg body wt) and killed at 3 and 12 hours after ethanol by gavage. The gene microarrays were compared with those made on the liver of rats from a previous study, in which the rats were fed ethanol by intragastric tube for 1 month (36% of calories derived from ethanol). Results:, Microarray analysis data varied between the acute and chronic models in several important respects. Growth factors increased mainly in the chronic alcohol fed rat. Changes in enzymes involved in oxidative stress were noted only with chronic ethanol feeding. Gene expression of fat metabolism was increased only with chronic ethanol feeding. Most importantly, epigenetic related enzymes and acetylation and methylation of histones changed only after chronic ethanol feeding. Conclusions:, The results support the concept that chronic ethanol ingestion induces altered gene expression as a result of changes in epigenetic mechanisms, where acetylation and methylation of histones were altered. [source] Hypoglycemic effect and chlorogenic acid content in two Cecropia speciesPHYTOTHERAPY RESEARCH, Issue 8 2005Pilar Nicasio Abstract The hypoglycemic effect of methanol leaf extracts from Cecropia obtusifolia and C. peltata was evaluated in healthy mice. A significant decrease (p < 0.05) in plasma glucose levels was recorded 2 and 4 h after a single oral administration of methanol extracts (1 g/kg). This effect was correlated with the chlorogenic acid contents in both species; C. peltata, containing 19.84 ± 1.64 mg of chlorogenic acid/g of dried leaves produced the highest decrease (D, 2,60 = 20.18, p < 0.05) of plasma glucose levels (52.8%). The extracts of C. obtusifolia from Tabasco and Veracruz, showed similar hypoglycemic effects (33.3% and 35.7%, respectively) and chlorogenic acid contents (Tukey0.05 = 1.8859) (13.3 ± 3.2 mg/g and 13.1 ± 1.6 mg/g, respectively). The hypoglycemic effect produced by different doses (0.1, 0.25, 0.50, 0.75 and 1 g/kg body wt, p.o.) of C. peltata showed a lineal relationship with chlorogenic acid content, reaching an ED50 = 0.540 g/kg body wt for extract, and an ED50 = 10.8 mg/kg body wt for chlorogenic acid. These results suggest that C. peltata is a better hypoglycemic agent than C. obtusifolia, and it could be considered for developing a phytomedicinal product to carry out clinical trials. Copyright © 2005 John Wiley & Sons, Ltd. [source] Functional significance of hepatic arterial flow reserve in patients with cirrhosisHEPATOLOGY, Issue 2 2003Alexander Zipprich In cirrhosis, hepatic arterial vasodilatation occurs in response to reduced portal venous blood flow. However, although the hepatic arterial flow reserve is high in patients with cirrhosis, its impact on hepatic function is unknown. This study investigated the effect of adenosine-induced hepatic arterial vasodilatation on different markers of liver function. In 20 patients with cirrhosis (Child-Pugh class A/B/C: n = 2/7/11) adenosine (2-30 ,g · min,1 · kg body wt,1) was infused into the hepatic artery and hepatic arterial average peak flow velocities (APV), pulsatility indices (PI), and blood flow volumes (HABF) were measured using digital angiography and intravascular Doppler sonography. Indocyanine green (ICG), lidocaine, and galactose were administered intravenously in doses of 0.5, 1.0, and 500 mg/kg body weight in the presence of adenosine-induced hepatic arterial vasodilatation and, on a separate study day, without adenosine. ICG disappearance, galactose elimination capacity (GEC), and formation of the lidocaine metabolite monoethylglycinxylidide (MEGX) were assessed. Adenosine markedly increased APV and HABF and markedly decreased PI. Serum MEGX concentrations were 63.7 ± 18.2 (median, 62; range, 36-107) and 99.0 ± 46.3 (82.5; 49-198) ng/mL in the absence and presence of adenosine infusion, respectively (P = .001). Adenosine-induced changes in MEGX concentrations were correlated inversely to changes in APV (r = ,0.5, P = .02) and PI (r = ,0.55, P = .01) and were more marked in Child-Pugh class C compared with Child-Pugh class A patients (57.4 ± 49.9 [44; ,14 to 140] vs. 8.4 ± 16.5 [13; ,11 to 35] ng/mL, P < .01). In conclusion, hepatic arterial vasodilatation provides substantial functional benefit in patients with cirrhosis. The effect does not depend directly on hepatic arterial macroperfusion and is observed preferentially in patients with decompensated disease. [source] Protective effect of the cruciferous vegetable mustard leaf (Brassica campestris) against in vivo chromosomal damage and oxidative stress induced by ,-radiation and genotoxic chemicalsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2008Ashu B. Tiku Abstract We evaluated the possible protective effect of the popular Indian cruciferous vegetable mustard leaf (Brassica campestris) against chromosomal damage and oxidative stress induced by ,-radiation, cyclophosphamide (CPH) and urethane (URE), in mice. In vivo bone marrow micronucleus test was performed to assess chromosomal damage, and oxidative stress was monitored by estimating the changes in lipid peroxidation and the status of glutathione (GSH) as well as redox cycle antioxidants. Pretreatment with 50,250 mg/kg body wt of mustard leaf extract (MLE) for seven days significantly reduced the frequencies of micronuclei induced by ,-radiation, CPH and URE. The protective effect against chromosomal damage was associated with modulation of lipid peroxidation as well as an increase in GSH and the GSH-dependent enzyme glutathione S -transferase (GST). Mass spectral analysis showed the presence of glucosinolates in MLE used for the pretreatment of mice. These findings indicate that intake of the green leafy cruciferous vegetable mustard leaf can lead to protection against in vivo genotoxicity and oxidative stress. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficitsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Qun Wang Abstract Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death. © 2005 Wiley-Liss, Inc. [source] Hypoglycemic effect and chlorogenic acid content in two Cecropia speciesPHYTOTHERAPY RESEARCH, Issue 8 2005Pilar Nicasio Abstract The hypoglycemic effect of methanol leaf extracts from Cecropia obtusifolia and C. peltata was evaluated in healthy mice. A significant decrease (p < 0.05) in plasma glucose levels was recorded 2 and 4 h after a single oral administration of methanol extracts (1 g/kg). This effect was correlated with the chlorogenic acid contents in both species; C. peltata, containing 19.84 ± 1.64 mg of chlorogenic acid/g of dried leaves produced the highest decrease (D, 2,60 = 20.18, p < 0.05) of plasma glucose levels (52.8%). The extracts of C. obtusifolia from Tabasco and Veracruz, showed similar hypoglycemic effects (33.3% and 35.7%, respectively) and chlorogenic acid contents (Tukey0.05 = 1.8859) (13.3 ± 3.2 mg/g and 13.1 ± 1.6 mg/g, respectively). The hypoglycemic effect produced by different doses (0.1, 0.25, 0.50, 0.75 and 1 g/kg body wt, p.o.) of C. peltata showed a lineal relationship with chlorogenic acid content, reaching an ED50 = 0.540 g/kg body wt for extract, and an ED50 = 10.8 mg/kg body wt for chlorogenic acid. These results suggest that C. peltata is a better hypoglycemic agent than C. obtusifolia, and it could be considered for developing a phytomedicinal product to carry out clinical trials. Copyright © 2005 John Wiley & Sons, Ltd. [source] The antiulcer activity of Garcinia cambogia extract against indomethacin-induced gastric ulcer in ratsPHYTOTHERAPY RESEARCH, Issue 1 2002P. Mahendran Abstract Garcinia cambogia extract is a herbal preparation that has been suggested as useful in the treatment of gastrointestinal disorders. In the present study this drug was tested for its antiulcerogenic effect. Oral pretreatment with Garcinia cambogia fruit extract (1,g/kg body wt/day) for 5, 10 or 15 days protected the gastric mucosa against the damage induced by indomethacin (20,mg/kg body wt). The volume and acidity of the gastric juice decreased in the pretreated rats. The glycoprotein levels of the gastric contents which were decreased in the untreated rats, maintained near normal levels in the pretreated rats. Protein which was elevated in the gastric juice of untreated rats, showed near normal levels in the pretreated rats. Garcinia cambogia was able to decrease the acidity and to increase the mucosal defence in the gastric areas, thereby justifying its use as an antiulcerogenic agent. Copyright © 2002 John Wiley & Sons, Ltd. [source] |