Pioglitazone: a promising therapeutic tool in sodium taurocholate-induced severe acute pancreatitis.
BACKGROUND
Studies suggest that peroxisome proliferator-activated receptor γ(PPARγ) ligands may represent a therapeutic option in acute pancreatitis, yet most of them have been prophylactic administrated.


OBJECTIVE
To evaluate the therapeutic effect of pioglitazone in rats with severe acute pancreatitis induced by sodium taurocholate.


METHODS
Severe acute pancreatitis (SAP) was induced in male Sprague-Dawley rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. After SAP was induced, pioglitazone was injected intraperitoneally and its role on the severity of inflammatory response and pancreatic injury was investigated. Amylase activity, inflammatory cytokines production, pathological changes of pancreas, PPARγ mRNA expression, and the survival rate were examined.


RESULTS
Treatment with pioglitazone decreased the level of amylase activity, proinflammatory factors IL-6 and TNF-α, ameliorated pancreatic histological score, and upregulated the expression of PPARγ mRNA. The survival rate in the early stage of severe acute pancreatitis was also improved.


CONCLUSIONS
Pioglitazone can be used as a therapeutic drug and relieve the damages caused by SAP, which suggests PPARγ ligand-pioglitazone offers a potent approach for the treatment of severe acute pancreatitis.
Xu
Ping
P
Department of Gastroenterology, Branch Hospital of the First People's Hospital, Shanghai Jiao Tong University, School of Medicine, 201600, Shanghai, China. yfyxp@yahoo.com.cn
Xu
Kai
K
Wang
Jing
J
Jiang
Jin-Ping
JP
Chen
Ling-Quan
LQ
D000681:Amylases / Q000096:biosynthesis; D000818:Animals; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D047495:PPAR gamma / Q000819:agonists; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013656:Taurocholic Acid / Q000009:adverse effects; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007004:Hypoglycemic Agents; D015850:Interleukin-6; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D013656:Taurocholic Acid; D000681:Amylases; D000077205:Pioglitazone
ANZ J Surg. 2004 Apr;74(4):218-21
15043731
Diabetologia. 1999 Jun;42(6):702-10
10382590
Intensive Care Med. 2004 May;30(5):951-6
14985957
World J Gastroenterol. 2007 Apr 7;13(13):1983-8
17461502
Gut. 1998 Sep;43(3):408-13
9863488
J Immunol. 2003 Dec 15;171(12):6827-37
14662889
Am J Respir Cell Mol Biol. 2001 Jun;24(6):688-93
11415933
J Immunol. 2004 Oct 15;173(8):5196-208
15470065
Mol Cell Biochem. 2001 Aug;224(1-2):29-37
11693197
Endocrinology. 1997 Jul;138(7):3073-6
9202256
World J Gastroenterol. 2005 Sep 14;11(34):5309-13
16149137
Am J Surg. 1996 Feb;171(2):274-80
8619467
Scand J Gastroenterol Suppl. 1996;219:43-6
8865471
Acta Pharmacol Sin. 2006 Sep;27(9):1146-52
16923334
Ann Surg. 1992 Jan;215(1):44-56
1731649
J Pharmacol Exp Ther. 2003 Sep;306(3):846-54
12805475
World J Gastroenterol. 2006 Oct 28;12(40):6458-63
17072978
Lancet. 1999 Jul 10;354(9173):141-8
10408502
Arch Med Res. 2009 Feb;40(2):79-88
19237016
Gastroenterology. 2003 May;124(5):1315-24
12730872
Mol Cell Biol. 2000 Jul;20(13):4699-707
10848596
Nature. 1998 Jan 1;391(6662):79-82
9422508
Nature. 1998 Jan 1;391(6662):82-6
9422509
World J Gastroenterol. 2005 Oct 28;11(40):6322-9
16419161
Pancreas. 2003 Jul;27(1):58-66
12826907
Br J Surg. 1996 Mar;83(3):349-53
8665189
J Gastrointest Surg. 2006 Sep-Oct;10(8):1120-30
16966031
Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E201-7
14701665
Gastroenterology. 1997 Mar;112(3):960-7
9041259
Gastroenterology. 1997 Nov;113(5):1741-6
9352880