Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats

Jia-Sheng Zhao, Feng-Shang Zhu, Su Liu, Chang-Qing Yang, Xi-Mei Chen
Chinese Medical Journal 2012, 125 (13): 2316-21

BACKGROUND: Pioglitazone is effective in nonalcoholic steatohepatitis (NASH), but the mechanisms of action are not completely understood. This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenases-2 (COX-2) expression in NASH rats.

METHODS: Thirty Sprague-Dawley male rats were randomly assigned to a control group (n = 10), NASH group (n = 10), and pioglitazone treatment group (n = 10). Liver tissues were processed for histology by hematoxylin & eosin and Masson stained. Serum alanine aminotransferase (ALT), cholesterol, triglyceride, fasting blood glucose (FBG), fasting insulin (FINS) levels and biochemical parameters of antioxidant enzyme activities, tumor necrosis factor alpha (TNF-α), prostaglandin E(2) (PGE(2)) levels in serum and liver were measured. The mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARγ), NF-κB and COX-2 were determined by real-time polymerase chain reaction, Western blotting and immunohistochemistry. One-way analysis of variance (ANOVA) and Wilcoxon's signed-rank test was used for the statistical analysis.

RESULTS: There were severe steatosis, moderate inflammatory cellular infiltration and fibrosis in NASH rats. After pioglitazone treatment, steatosis, inflammation and fibrosis were significantly improved compared with the NASH group (χ(2) = 20.40, P < 0.001; χ(2) = 20.17, P < 0.001; χ(2) = 13.98, P = 0.002). Serum ALT, cholesterol, triglyceride, FBG, FINS levels were significantly elevated in the NASH group (P < 0.05). In the NASH group, total anti-oxidation competence (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels in serum and liver were conspicuous disordered than those parameters in the control group. Meanwhile, TNF-α and PGE(2) levels in serum and liver were significantly increased compared with the control group. Immunohistochemistry showed NF-κB and COX-2 expression in liver was significantly elevated. However, PPAR? level was decreased in the NASH group. Real-time PCR and Western blotting revealed mRNA and protein expression of COX-2 were increased in the NASH group compared with the control group (0.57 ± 0.08 vs. 2.83 ± 0.24; 0.38 ± 0.03 vs. 1.00 ± 0.03, P < 0.001 and P = 0.004, respectively). After pioglitazone intervention, all of those parameters markedly improved (P < 0.05 or P < 0.01).

CONCLUSION: Down-regulating hepatic NF-κB and COX-2 expression, at least in part, is one of the possible therapeutic mechanisms of pioglitazone in NASH rats.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"