JOURNAL OF PRACTICAL HEPATOLOGY ›› 2014, Vol. 17 ›› Issue (2): 163-167.doi: 10.3969/j.issn.1672-5069.2014.02.013

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Effects of pentoxifylline on ethanol metabolic enzymes and peroxisome proliferator-activated receptor alpha in mice with alcoholic liver disease

Qu Yaoning,Dong Lei,Shi Haitao,et al.   

  1. Department of Gastroenterology,Second Affiliated Hospital,Medical College,Jiaotong University,Xi’an 710004,China
  • Received:2013-09-06 Online:2014-08-20 Published:2016-04-15

Abstract: Objective To investigate the effect of pentoxifylline (PTX) on ethanol metabolic enzymes and peroxisome proliferator-activated receptor alpha (PPAR-α) in C57BL/6 mice with alcoholic liver disease. Methods Sixty-four mice were randomly divided into alcoholic liver disease model, PTX intervention and control group; Acute alcoholic liver injury was induced in mice by intragastric administration with 50% alcohol,and chronic alcoholic liver injury was induced by intragastric administration with 20% alcohol daily for six weeks;Serum alcohol dehydrogenase(ADH) and cytochrome P4502E1 (CYP2E1) activity was measured by colorimetric method;The mRNA levels of ADH,CYP2E1 and PPAR-α were measured by PT-PCR;The protein expression of CYP2E1 and PPAR-α was determined by immunohistochemistry. Results The serum activity of ADH did not differ among mice with acute[(11.2±1.6)U/ml] or chronic[(5.8±1.4) U/ml] alcoholic liver injury and controls[(12.5±1.2)U/ml and(4.3±0.6)U/ml,respectively];In mice with acute and chronic liver injury,the CYP2E1 activity was(12.2±1.8)U/ml and (11.8±1.7) U/ml,respectively,significantly higher than those in normal controls[(7.9±1.4)U/ml and (6.5±1.2) U/ml,P<0.01)] and those in PTX-intervented mice [(8.1±1.5) U/ml and (7.8±1.5)U/ml,P<0.01];The relative CYP2E1 positive cells in liver tissues in mice with acute and chronic alcoholic liver injury were (765±21) and (682±25),respectively,significantly higher than those in normal controls [(308±12) and (305±18),P<0.01)] and in mice with high-dosage of PTX intervention [(521±18) and (418±12),respectively,P<0.01];The mRNA levels of ADH in liver tissues of mice with acute and chronic alcoholic liver injury were similar to that in the controls, however, the relative CYP2E1 mRNA levels[(1.47±0.32) and (1.13±0.52)] were significantly higher than those in normal controls [(0.89±0.23) and (0.45±0.28),respectively,P<0.01)] and in mice with high-dose of PTX[(0.92±0.27) and (0.48±0.32),respectively,P<0.01)];PPAR-α mRNA levels in liver tissues did not differ among mice with acute liver injury and normal controls,however,it was significantly lower than that in normal controls(0.85±0.21) in liver of mice with chronic alcoholic liver injury[(0.45±0.31),P<0.05];The PPAR-α positive cells in mice of acute and chronic alcohol injury were (322±15) and(262±23),respectively,significantly higher than those in normal controls[(721±18)and (689±14),P<0.01] and in mice with high-dose of PTX intervention[(548±20) and (725±19),P<0.01]. Conclusion PTX attenuates acute or chronic alcoholic liver injury,probably by through up-regulation of CYP2E1 and down-regulation of PPAR-α.

Key words: Alcoholic liver disease, Ethanol metabolic enzymes, Pentoxifylline, Peroxisome proliferator-activated receptor alpha, Mice