The Effect Of A Selective COX-2 Inhibitor Celecoxib On Rats With Acute Or Chronic Liver Injury Induced By Alcohol

Objective To investigate the effect of selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on rats with acute or chronic liver injury induced by alcohol, the models of rats with acute and chronic liver injury induced by alcohol were established. The damage of liver tissue, the changes of prooxidant/antioxidant system in rats and the expression of COX-2 in liver tissue were evaluated among three groups of rat medols.Methods 1. Establish of rat models The model of acute and chronic liver injury rats induced by alcohol were established through manned intragastric injection, meanwhile these rats were fed by standard food. The acute group: 22 male Wistar rats were randomly divided into three groups. Control group (n=6) were treated with dextrose, liver injury group(n=8) with ethanol, treatment group (n=8) with ethanol plus a selective COX-2 inhibitor as celecoxib. The chronic group: 58 male Wistar rats were randomly divided into three groups. Control group (n=10) were treated with corn oil plus dextrose, liver injury group(n=24) with corn oil plus ethanol, treatment group(n=24) with corn oil plus ethanol andethanol and celecoxib. 2. Collection of specimens The model rats' liver tissue, serum, plasma were havested and preserved in -70 C refrigerator. 3. Measurement of specimens The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, malondialdehyde (MDA) in liver and plasma, 6-keto-prostaglandin Fl alpha (6-k-PGF1) and thromboxane B2 (TXB2) in liver and activity of glutathione s-transferase (GST) and superoxide dismutase (SOD) i n 1 iver a nd p lasma w ere m easured. H istopathology o f 1 iver t issue w as analyzed by light microscope and electron microscope, and in the mean time the COX-2 expression in liver tissue was detected by imniunohistochemistry and Western blot.Results 1. Acute liver injury induced by alcohol(1) The level of AST and ALT in serum was not significantly changed among control group, liver injury group and treatment group (P > 0.05).(2) GST and SOD activity in liver tissue and plasma were significantly decreased in the liver injury group compared with those in the control group (P< 0.01 or P < 0.05), but were not significantly decreased compared with those in the treatment group (P > 0.05). Liver tissue MDA level in the liver injury group was significantly increased compared with that in the control group (P < 0.01), but was not significantly increased compared with that in the treatment group (P> 0.05). There were no significant change in plasma MDA level among the control group, liver injury group and treatment group (P > 0.05).(3) The level of 6-k-PGF1 in liver tissue in liver injury group was significantly increased compared with those in the control group and in the treatment group (P < 0.05). The level of TXB2 in liver tissue in liver injury group was not significantly increased compared with those in the control groupand in the treatment group (P > 0.05).(4) Liver histological analysis: Light microscope showed that there were no obvious hepatocytes' injury among the three groups.(5) The expression of COX-2: Immunohistochemistry staining demonstrated that the expression of COX-2 in the three groups was all negative.2. Chronic liver injury induced by alcohol(1) The serum AST level in the liver injury group was significantly increased compared with that in the control group and in the treatment group (P< 0.01) . The serum ALT level in the liver injury group was significantly increased compared with that in the control group (P < 0.01), but was not significantly increased compared with that in the treatment group (P > 0.05).(2) The plasma GST activity and the liver tissue MDA level in liver injury group were significantly increased compared with those in the control group (P < 0.05), but were not significantly increased compared with those in the treatment group (P > 0.05).The activity of GST and SOD in liver tissue and SOD in plasma in liver i...