Genetic factors in acute pancreatitis

Abstract

s / Pancreatology Aims: Since ursodeoxycholic acid (UDC) is known to protect the mitochondria against hydrophobic bile acids and have antiapoptotic effect, we investigated whether UDC is able to prevent the CDC-induced cell damage. Materials & methods: Inta-interlobular ducts were isolated from guinea pig pancreas. Ducts were then pretreated with UDC (0.1 mM and 0.5mM) for 5 h and 24 h and changes in intracellular Ca2+concentration [Ca]i, ATP level [ATP]i, pH [pH]i, mitochondrial permeability transition pore (MPTP) opening were measured by microfluorometry. Mitochondrial transmembrane potential (MTP) was studied by confocal microscopy. Morphological changes of mitochondria were investigated by transmission electron microscopy. Expressions of bile acid transporters were studied by reverse transcriptase PCR (RT-PCR). Results: 24 h pretreatment with 0.5 mM UDC significantly reduced the rate of ATP depletion, mitochondrial injury, MPTP opening and the decrease of MTP induced by 1mM CDC. In addition, 0.5 mMUDC prevented the inhibitory effect of CDC on the acid-base transporters, however, had no effect on the CDC-induced calcium signaling. mRNA expression of Slc10A1 and A2 was detected in the ducts by RT-PCR. Conclusion: Our results indicate that protection of mitochondria with UDC administrationmay represent a novel option against bile acid-induced ductal injury. This study was supported by Hungarian National Development Agency grants (T AMOP-4.2.2.A-11/1/KONV-2012-0035, T AMOP-4.2.2-A-11/1/ KONV-2012-0052, T AMOP-4.2.2.A-11/1/KONV-2012-0073, T AMOP-4.2.2./ B-10/1-2010-0012, T AMOP 4.2.4.A/2-11-1-2012-0001 ‘National Excellence Program) and the Hungarian Scientific Research Fund (OTKA NF105758, NF100677, K109756)