[Effects of pentoxifylline on hepatic nuclear factor-kappa B signaling pathway and insulin resistance in nonalcoholic steatohepatitis rats induced by fat-rich diet].
OBJECTIVE
To explore the effects of pentoxifylline (PTX) on nuclear factor-kappa B (NF-kB) signaling pathway, insulin receptor substrates (IRSs) and glucose transporter 2 (GLUT2) expressions in livers in a rat model of nonalcoholic steatohepatitis (NASH).


METHODS
Rats fed a fat-rich diet for 4 weeks were randomly allocated into two groups; the model group rats (n = 12) were fed a high-fat diet alone and the PTX group rats (n = 12) were fed a high-fat diet plus PTX (100 mg x kg(-1)/d(-1)) in drinking water. Meanwhile, rats (n = 6) fed a standard diet from the start served as controls. All the rats were sacrificed at the end of the 24th week. Hepatic NF-kappaB binding activity was measured by electrophoretic mobility shift assay (EMSA). The expression of tumor necrosis factor (TNF) alpha and inhibitor kappaB (IkappaBalpha) proteins in livers were determined by Western blot. Messenger RNA of IRS-1, IRS-2 and GLUT2 expressions were examined by RT-PCR.


RESULTS
NF-kappaB binding activity was higher in the model group than that in the controls, while it was lower in the PTX group compared with that in the model group. The expression of TNFalpha protein was markedly increased in the model group (vs. the control group) but decreased in the PTX group (vs. the model group). The expression of IkappaBaalpha protein was decreased in the model group (vs. the control group) but increased in the PTX group (vs. the model group) to a certain extent. IRS-2 mRNA expression was markedly increased in the model group, and significantly decreased in the PTX group when compared with the model group (P less than 0.01).


CONCLUSIONS
PTX could influence NF-kappaB signaling pathway and IRS expression in livers of NASH rats, which might be involved in the improvement of hepatic insulin resistance.
Fan
Jian-Gao
JG
Center for Fatty Liver, Shanghai First People's Hospital, Jiaotong University, Shanghai 200080, China.
Qian
Yan
Y
Zheng
Xiao-Ying
XY
Cai
Xiao-Bo
XB
Lu
Yuan-Shan
YS
D000818:Animals; D005234:Fatty Liver / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051273:Glucose Transporter Type 2; D020672:I-kappa B Proteins; D055504:Insulin Receptor Substrate Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; C495683:Slc2a2 protein, rat; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D010431:Pentoxifylline