[RETRACTED ARTICLE] Therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis

Abstract

Caspase recruitment domain-containing protein 9 (Card9) is located upstream of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) inflammatory pathways. This study investigated the therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis (SAP). SAP was induced by a retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct of Sprague Dawley rats (n=54), which were then treated with pioglitazone. Blood and pancreatic tissues were harvested at 3, 6, and 12 h after SAP induction. Pancreatic pathological damage was evaluated by hematoxylin and eosin staining. Serum amylase, serum pro-inflammatory cytokines, and pancreatic myeloperoxidase (MPO) activities were determined by enzyme-linked immunosorbent assay. The expression of Card9 mRNA and protein in pancreatic tissues was detected by real-time polymerase chain reaction and western blotting. Pioglitazone had a therapeutic effect in treating rats with SAP by decreasing the level of amylase activity, ameliorating pancreatic histological damage, decreasing serum pro-inflammatory cytokine levels and tissue MPO activity, and downregulating the expression of NF-κB, p38MAPK, and Card9 mRNAs and proteins (P<0.05). The present study demonstrated that the inhibition of Card9 expression could reduce the severity of SAP. Card9 has a role in the pathogenic mechanism of SAP.

Curcumin Attenuates Inflammation in a Severe Acute Pancreatitis Animal Model by Regulating TRAF1/ASK1 Signaling

“…It was reported that activated NF-κB translocates to nuclei to initiate its targeted down-stream genes encoding proinflammatory cytokines, including interleukins (IL) and tumor necrosis factors (TNF) [ 17 ]. In the present study, we found that the nuclear translocation of NF-κB was dramatically up-regulated in SAP pancreases, which is consistent with the observations reported by previous studies [ 14 , 18 ]. MAPKs are important protein kinases that play roles in responding to harmful pathological stress [ 19 ].…”

“…When AP develops into SAP, it is a life-threatening condition with severe complications and high mortality [ 14 ]. Inflammatory responses and cascade activation contribute to the high mortality of SAP by inducing systematic inflammatory response syndrome (SIRS) and MODS [ 15 ].…”

Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats

“…In their study pioglitazone enhanced glomerular filtration after injury by reducing of COX-2 expression 26 . Beside this, treatment with pioglitazone inhibited the activation of the NF-κB and MAPK inflammatory signaling pathways and reduced significantly the secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 27 .…”

Effects of intestinal lymphatic ligation on intestinal immunity in rats with severe acute pancreatitis

“…These findings clarified that ligation of the mesenteric lymph duct promotes the increase in these cytokines by blocking the translocation of inflammatory cytokines via the mesenteric lymph duct. MPO is a biochemical marker for neutrophil infiltration in studies of multiple organ injury in SAP, and its activity is related to the severity of intestine injury [33]. The present results showed that the increase in intestine MPO indicated the progressive aggravation of SAP‐associated intestine injury (Fig.…”