Title |
CILOSTAZOL HEPATOPROTECTIVE EFFECT AGAINST ISCHEMIA/REPERFUSION: INVOLVEMENT OF GSK-3β, CYCLIN D1 and WNT/β-CATENIN PATHWAY |
| J Pharmacol Res Vol:4 Iss:1 (2014-04-01) : 75-81 |
Authors |
GENDY A., EL-ABHAR H., MOHSEN A.R. |
Published on |
01 Apr 2014 Pages : 75-81 Article Id : BIA0002181 Views : 1031 Downloads : 574 |
DOI | http://dx.doi.org/10.9735/0976-7134.4.1.75-81 |
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Abstract |
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Cilostazol is an antiplatelet that acts by inhibiting phosphodiesterase-3 and that was proven to be effective in models of ischemia/reperfusion (I/R) injury; however, its possible role in hepatic I/R remains indistinct, which is the aim of the current work. To fulfill this goal, rats were randomized into sham, I/R and cilostazol (60mg/kg, p.o) groups. The hepatic artery and portal vein to the left and median liver lobes were occluded for 30 min and then declamped for reperfusion to establish a model of segmental (70%) warm hepatic ischemia. Pretreatment of animals with cilostazol for two weeks prior to I/R insult significantly decreased serum alanine aminotransferase, and inhibited I/R-induced hepatocytes apoptotic death signified by inhibition of caspase-3. Moreover, cilostazol increased ATP content and lowered the level of lipid peroxidation assessed as malondialdehyde. The drug also elevated the nitric oxide content and decreased that of tumor necrosis factor-α, as well as the myeloperoxidase activity, a marker of neutrophil infiltration. Mechanistic studies revealed that cilostazol protected the liver and enhanced its proliferation ability, where it markedly increased the level of β-catenin and cyclin D1, but blocked the phosphorylation of GSK-3β at Ser9. In conclusion, cilostazol pre-administration protected hepatocytes against I/R insult by virtue of its antioxidant, anti-inflammatory, and antiapoptotic effects; besides, the drug increased hepatocytes proliferation by increasing the level of cyclin D1. It increased also the Wnt/ β-catenin pathway, which aid in its hepatoprotective action along with blocking the GSK-3β phosphorylation at the ser9, which had injurious role in this work.
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Title |
PREVENTIVE EFFECTS OF Arabidopsis thaliana EXTRACT ON LIVER DAMAGE OF DIABETIC MICE INDUCED BY ALLOXAN |
| J Pharmacol Res Vol:4 Iss:1 (2014-04-22) : 82-86 |
Authors |
RASHID K.I., KAMEL A.M., BAKIR T.Y. |
Published on |
22 Apr 2014 Pages : 82-86 Article Id : BIA0002228 Views : 1020 Downloads : 802 |
DOI | http://dx.doi.org/10.9735/0976-7134.4.1.82-86 |
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Abstract |
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This study was carried out in March/2013 in the College of Medicine - Baghdad University to determine the effects of Arabidopsis thaliana seed extract on blood glucose levels and liver damage of induced diabetic mice by alloxan. Results showed that the treatment with 200 mg/kg of body weight led to significant reduction in blood glucose levels after 3 to 12 days of treatment. This reduction revealed that the seed extract of Arabidopsis thaliana have hyperglycemic activity as compared to the control (untreated) animals. On the other hand, the Arabidopsis-treated diabetic group of mice showed normal hepatic architecture which was similar to that of untreated group (control) and they have few PAS positive granules, and most of the hepatocytes were studded with PAS positive granules. The Arabidopsis-treated diabetic group showed that hepatocytes were studded with bluish granules, while those of untreated diabetic group showed fewer bluish granules in the cytoplasm. It was observed the accumulation of lipoid droplets in the cytoplasm of hepatocytes of diabetic group. This change was reminiscent to the formation of fatty liver due to the increased of fatty acids into the liver induced by hypoinsulinemia. Also it was observed a reduction in glycogen in the liver cells of diabetic group as compared to the Arabidopsis-treated group which indicates that Arabidopsis extract stimulated protein synthesis by increasing the number of ribosomes, and improving the insulin resistance. Finally, Arabidopsis consumption have hypoprotective role in diabetic mice and offers promising perspective deserve further investigation.
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