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Pioglitazone attenuates ischemia/reperfusion-induced liver injury in rats.
Transplant Proc. 2009 Dec; 41(10):4105-9.TP

Abstract

INTRODUCTION

Hepatic ischemia/reperfusion (I/R) injury leads to free radical generation and acute inflammatory responses that cause liver damage, an important problem for liver transplantation. Pioglitazone is known to protect I/R injury in various tissues; however, the mechanism of cytoprotection is not well understood. This study investigated the effects of pioglitazone administration in a warm hepatic I/R model on tumor necrosis factor (TNF)-alpha level, tissue injury, and antioxidant enzyme activity.

MATERIALS AND METHODS

Eighty wistar strain rats were divided into 4 groups (n = 20): Group 1 sham hosts; Group 2 hepatic I/R; Group 3 hepatic I/R + pioglitazone (10 mg/kg); and Group 4 hepatic I/R + vehicle. Rat livers were subjected to 30 minutes of ischemia followed by 6 hours of reperfusion. After reperfusion rats were humanely killed to obtain liver tissue to study glutathione peroxidase (GPx), superoxide dysmutase (SOD), malondialdehyde (MDA) levels and for histopathologic assessment. TNF-alpha, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in serum.

RESULTS

Pioglitazone pretreatment significantly reduced liver enzyme content (ALT, 176.80 +/- 13.75 vs 235.28 +/- 31.92 and AST, 748.20 +/- 79.29 vs 944.85 +/- 101.87) and TNF-alpha level (9:8.60 +/- 8.67 vs 138.28 +/- 9.99) after I/R compared with the control group. MDA level (3.02 +/- 0.37 vs 4.36 +/- 0.38) and hepatocytic degeneration were reduced in the pioglitazone-treated group. GPx (2.40 +/- 0.25 vs 1.36 +/- 0.31) and SOD activity (2.22 +/- 0.30 vs 1.40 +/- 0.35) were significantly higher in the pioglitazone-treated group compared with the control group.

CONCLUSION

The present study showed that pioglitazone administration improved hepatic I/R injury that was associated with enhanced antioxidant enzyme activities and suppression of TNF-alpha, ALT, and AST levels. Because peroxisome proliferator-activated receptor-gamma agonists are widely used to treat diabetic patients, it may be relatively easy to expand their clinical indication. However, further investigations will be required to delineate protective mechanisms by which pioglitazone attenuates hepatic tissue injury after I/R.

Authors+Show Affiliations

Liver and Gastroenterology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20005349

Citation

Somi, M H., et al. "Pioglitazone Attenuates Ischemia/reperfusion-induced Liver Injury in Rats." Transplantation Proceedings, vol. 41, no. 10, 2009, pp. 4105-9.
Somi MH, Hajipour B, Asl NA, et al. Pioglitazone attenuates ischemia/reperfusion-induced liver injury in rats. Transplant Proc. 2009;41(10):4105-9.
Somi, M. H., Hajipour, B., Asl, N. A., Estakhri, R., Azar, A. N., Zade, M. N., Haghjou, A. G., & Vatankhah, A. M. (2009). Pioglitazone attenuates ischemia/reperfusion-induced liver injury in rats. Transplantation Proceedings, 41(10), 4105-9. https://doi.org/10.1016/j.transproceed.2009.09.075
Somi MH, et al. Pioglitazone Attenuates Ischemia/reperfusion-induced Liver Injury in Rats. Transplant Proc. 2009;41(10):4105-9. PubMed PMID: 20005349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pioglitazone attenuates ischemia/reperfusion-induced liver injury in rats. AU - Somi,M H, AU - Hajipour,B, AU - Asl,N A, AU - Estakhri,R, AU - Azar,A N, AU - Zade,M N, AU - Haghjou,A G, AU - Vatankhah,A M, PY - 2008/12/06/received PY - 2009/05/16/revised PY - 2009/09/15/accepted PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/4/24/medline SP - 4105 EP - 9 JF - Transplantation proceedings JO - Transplant Proc VL - 41 IS - 10 N2 - INTRODUCTION: Hepatic ischemia/reperfusion (I/R) injury leads to free radical generation and acute inflammatory responses that cause liver damage, an important problem for liver transplantation. Pioglitazone is known to protect I/R injury in various tissues; however, the mechanism of cytoprotection is not well understood. This study investigated the effects of pioglitazone administration in a warm hepatic I/R model on tumor necrosis factor (TNF)-alpha level, tissue injury, and antioxidant enzyme activity. MATERIALS AND METHODS: Eighty wistar strain rats were divided into 4 groups (n = 20): Group 1 sham hosts; Group 2 hepatic I/R; Group 3 hepatic I/R + pioglitazone (10 mg/kg); and Group 4 hepatic I/R + vehicle. Rat livers were subjected to 30 minutes of ischemia followed by 6 hours of reperfusion. After reperfusion rats were humanely killed to obtain liver tissue to study glutathione peroxidase (GPx), superoxide dysmutase (SOD), malondialdehyde (MDA) levels and for histopathologic assessment. TNF-alpha, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in serum. RESULTS: Pioglitazone pretreatment significantly reduced liver enzyme content (ALT, 176.80 +/- 13.75 vs 235.28 +/- 31.92 and AST, 748.20 +/- 79.29 vs 944.85 +/- 101.87) and TNF-alpha level (9:8.60 +/- 8.67 vs 138.28 +/- 9.99) after I/R compared with the control group. MDA level (3.02 +/- 0.37 vs 4.36 +/- 0.38) and hepatocytic degeneration were reduced in the pioglitazone-treated group. GPx (2.40 +/- 0.25 vs 1.36 +/- 0.31) and SOD activity (2.22 +/- 0.30 vs 1.40 +/- 0.35) were significantly higher in the pioglitazone-treated group compared with the control group. CONCLUSION: The present study showed that pioglitazone administration improved hepatic I/R injury that was associated with enhanced antioxidant enzyme activities and suppression of TNF-alpha, ALT, and AST levels. Because peroxisome proliferator-activated receptor-gamma agonists are widely used to treat diabetic patients, it may be relatively easy to expand their clinical indication. However, further investigations will be required to delineate protective mechanisms by which pioglitazone attenuates hepatic tissue injury after I/R. SN - 1873-2623 UR - https://www.unboundmedicine.com/medline/citation/20005349/Pioglitazone_attenuates_ischemia/reperfusion_induced_liver_injury_in_rats_ DB - PRIME DP - Unbound Medicine ER -