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Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats.
Chin Med J (Engl). 2012 Jul; 125(13):2316-21.CM

Abstract

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.

Authors+Show Affiliations

Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22882855

Citation

Zhao, Jia-Sheng, et al. "Pioglitazone Ameliorates Nonalcoholic Steatohepatitis By Down-regulating Hepatic Nuclear Factor-kappa B and Cyclooxygenases-2 Expression in Rats." Chinese Medical Journal, vol. 125, no. 13, 2012, pp. 2316-21.
Zhao JS, Zhu FS, Liu S, et al. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats. Chin Med J (Engl). 2012;125(13):2316-21.
Zhao, J. S., Zhu, F. S., Liu, S., Yang, C. Q., & Chen, X. M. (2012). Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats. Chinese Medical Journal, 125(13), 2316-21.
Zhao JS, et al. Pioglitazone Ameliorates Nonalcoholic Steatohepatitis By Down-regulating Hepatic Nuclear Factor-kappa B and Cyclooxygenases-2 Expression in Rats. Chin Med J (Engl). 2012;125(13):2316-21. PubMed PMID: 22882855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats. AU - Zhao,Jia-Sheng, AU - Zhu,Feng-Shang, AU - Liu,Su, AU - Yang,Chang-Qing, AU - Chen,Xi-Mei, PY - 2012/8/14/entrez PY - 2012/8/14/pubmed PY - 2012/12/29/medline SP - 2316 EP - 21 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 125 IS - 13 N2 - 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. SN - 2542-5641 UR - https://www.unboundmedicine.com/medline/citation/22882855/Pioglitazone_ameliorates_nonalcoholic_steatohepatitis_by_down_regulating_hepatic_nuclear_factor_kappa_B_and_cyclooxygenases_2_expression_in_rats_ L2 - https://Insights.ovid.com/pubmed?pmid=22882855 DB - PRIME DP - Unbound Medicine ER -