Acute Liver Injury and the Gut. Role of Nitric Oxide, and the Effect of Arginine and Probiotic Administration

University dissertation from Dept of Surgery, Malmö University Hospital, S-205 02 Malmö, Sweden

Abstract: Infectious complications with enteric bacteria are common in liver diseases and liver surgery. An increased bacterial translocation from the gut has been proposed as one underlying mechanism. In order to elucidate pathogenetic mechanisms and find possible preventive measures, we manipulated the enteric content and therefore we investigated the role of nitric oxide and the effect of arginine and probiotic administration on bacterial translocation, extent of liver injury and the associated intestinal mucosal changes in a D-galactosamine acute liver injury model. We showed that bacterial translocation could be one of the mechanisms potentiating the liver injury in this model of hepatotoxicity. Nitric oxide protects the liver from the acute injury. It reduces the liver injury and decreases bacterial translocation to the extraintestinal sites. Arginine has beneficial effects on the liver and reduces bacterial translocation. Nitric oxide production plays a role in the effects of arginine, but arginine can have effects on both liver and gut besides nitric oxide production. Modulation of the intestinal microflora by the administration of lactobacilli, reduces the potentially pathogenic Enterobacteriaceae count, bacterial translocation to extraintestinal sites and liver injury. The reduction of bacterial translocation and liver injury could be mediated via nitric oxide production. We have shown the importance of the gut and luminal factors in modulating the extent of the liver injury. It seems possible to alter the microecology of the gut by administration of probiotics and the addition of substrates, such as arginine, may locally influence the production of biological mediators. This can act as nutrition for the mucosa and host, but simultaneously give rise to pharmacologic actions both locally and at distant sites.

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