Experimental assessment of immunoreactivity indices and effectiveness of pharmacotherapy schemes in surgical models of acute pancreatitis of various severity

Introduction: The investigation was aimed at assessment of immunoreactivity in the experimental groups of animals and evaluation of effectiveness of different combinations of pharmacological drugs used in the surgical models for the treatment of acute pancreatitis (AP) of various degrees of severity. Materials and methods: As an object of research, sexually mature male individuals of mongrel white rats were used. Acute pancreatitis of various degrees of severity was caused by either a separate or simultaneous ligation of the pancreas ducts and an intraductal injection of the 50% bile solution in a dose of 0.2 mg/kg. Correction of immunoreactivity indices in the experimental animals was performed with the use of drug combinations producing immunomodulating, antioxidant and membrane protecting effects. Evaluation of the dynamics of immune parameters in rats was carried out using test systems from various manufacturers for laboratory analysis. The obtained findings were statistically processed with descriptive and variation techniques. Results and discussion: The rats developed AP of various degrees of severity, and differently expressed shifts in immunoreactivity indices were observed. Assessment of immune and oxidant indices in experimentally induced acute pancreatitis of moderate and severe states revealed metabolic and immune disorders with anti-inflammatory effects which had various degrees of expression. Combination of immunomodulators, antioxidants and membranoprotectors exerted positive effects on the immunoreactivity state, but insignificantly decreased the mortality rate in the groups of experimental animals. Conclusion: The combination of ferrovir, mexidol, phosphogliv, and its use for moderate and severe degrees of experimentally induced pancreatitis in rats decreases their mortality up to 12.9% and 19.8%. The combination of polyoxidonium, emoxipin and essentiale N exhibits positive clinico-laboratory effectiveness and lowers the mortality indices to statistically significant parameters – 11.8% и 19.6%, correspondingly, with p < 0.05.

A novel, protective role of ursodeoxycholate in bile-induced pancreatic ductal injury

We have previously shown that chenodeoxycholic acid (CDCA) strongly inhibits pancreatic ductal HCO3− secretion through the destruction of mitochondrial function, which may have significance in the pathomechanism of acute pancreatitis (AP). Ursodeoxycholic acid (UDCA) is known to protect the mitochondria against hydrophobic bile acids and has an ameliorating effect on cell death. Therefore, our aim was to investigate the effect of UDCA pretreatment on CDCA-induced pancreatic ductal injury. Guinea pig intrainterlobular pancreatic ducts were isolated by collagenase digestion. Ducts were treated with UDCA for 5 and 24 h, and the effect of CDCA on intracellular Ca2+ concentration ([Ca2+]i), intracellular pH (pHi), morphological and functional changes of mitochondria, and the rate of apoptosis were investigated. AP was induced in rat by retrograde intraductal injection of CDCA (0.5%), and the disease severity of pancreatitis was assessed by measuring standard laboratory and histological parameters. Twenty-four-hour pretreatment of pancreatic ducts with 0.5 mM UDCA significantly reduced the rate of ATP depletion, mitochondrial injury, and cell death induced by 1 mM CDCA and completely prevented the inhibitory effect of CDCA on acid-base transporters. UDCA pretreatment had no effect on CDCA-induced Ca2+ signaling. Oral administration of UDCA (250 mg/kg) markedly reduced the severity of CDCA-induced AP. Our results clearly demonstrate that UDCA 1) suppresses the CDCA-induced pancreatic ductal injury by reducing apoptosis and mitochondrial damage and 2) reduces the severity of CDCA-induced AP. The protective effect of UDCA against hydrophobic bile acids may represent a novel therapeutic target in the treatment of biliary AP.