Tryptophan metabolism in experimental necrotizing acute pancreatitis
Abstract
Pancreatic encephalopathy is a serious, often lethal complication of acute pancreatitis (AP). Its pathomechanism remains obscure. We have previously described increased blood levels of quinolinic acid (QUIN) – an endogeneous neurotoxine – during edematous experimental acute pancreatitis. Several other metabolites of tryptophan (TRP) are also known to be neuroactive. The aim of the present study was to assess tryptophan and its main metabolites: kynurenine (KYN), 3-hydroxykynurenine, quinolinic acid (QUIN), kynurenic acid (KYNA), serotonin (5HT) during experimental acute necrotizing acute pancreatitis. Experimental necrotizing acute pancreatitis was induced in rats by intraductal injection of 5% sodium taurocholate. Control groups consisted of sham-operated and not operated rats. The animals were sacrificed 5 and 24 hours after the operation. We evaluated -amylase, pancreas weight and histology as parameters of pancreatitis. A simplified neurological scoring system was applied. To assess TRP and its metabolites in plasma, we used high performance liquid chromatography. Five hours after the onset of AP we found significant increase in TRP metabolites: QUIN, KYNA, KYN, and 3HKYN in the plasma of animals with AP, as compared to the control group. When assessed 24 hours after induction of AP, those changes were no longer observed in blood. Instead, a decrease in TRP level appeared. Increase in plasma QUIN was associated with neurologic disturbances. In the present study we demonstrated transient activation of kynurenine pathway during early stages of experimental necrotizing AP, with increased blood levels of QUIN, KYNA, KYN, and 3HKYN and subsequent depletion of TRP. As some kynurenine derivatives, e.g. quinolinic acid, are endogenous toxins, they might contribute to neurologic and other organs disturbances during AP.
Keywords: acute pancreatitistryptophankynurenine3-hydroxykynureninekynurenic acidquinolinic acidserotonin
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