Pentoxifylline alleviates high-fat diet-induced non-alcoholic steatohepatitis and early atherosclerosis in rats by inhibiting AGE and RAGE expression.
OBJECTIVE
To investigate the expression of advanced glycation end products (AGEs) and their receptor RAGE in the livers and blood vessels of rats with non-alcoholic steatohepatitis (NASH) and the effect of pentoxifylline (PTX) on liver and artery function in rats with NASH.


METHODS
Sprague-Dawley rats were fed a high-fat diet for 12 weeks and given PTX by gavage for 4 weeks. The effects of PTX on hepatic liver and vessel function as well as the expression of AGE and RAGE in rats with NASH were assessed. The intima-media thickness (IMT) of the aorta and carotid artery was evaluated using ultrasonography.


RESULTS
Serum aspartic aminotransferase (AST) and blood levels of glucose (GLU) were reduced in the PTX group relative to the NASH group. The IMT of the aorta and carotid artery was increased in the NASH group compared with the control group. The IMT was reduced in NASH rats after treatment with PTX. Rats with NASH demonstrated higher AGE and RAGE protein levels in the liver and arteries compared with those of control rats. PTX treatment in NASH rats resulted in a decrease in AGE and RAGE protein levels in the liver and arteries compared with those in the NASH group.


CONCLUSIONS
Early atherosclerosis was observed in rats with NASH induced by a 16-week high-fat diet. High expression of AGE and RAGE in the livers and arteries of rats with NASH may contribute to the pathogenesis of NASH and early atherosclerosis. PTX showed protective effects on hepatic and arterial function, partially through inhibition of AGE and RAGE expression.
Wu
Jing
J
Department of Pathophysiology, Capital Medical University, Beijing, China.
Zhao
Miao-yun
MY
Zheng
Hao
H
Zhang
Hua
H
Jiang
Ying
Y
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004041:Dietary Fats / Q000008:administration & dosage*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
D004041:Dietary Fats; D017127:Glycation End Products, Advanced; D010726:Phosphodiesterase Inhibitors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D010431:Pentoxifylline