Glutamine treatment attenuates the development of organ injury induced by zymosan administration in mice

Abstract

Glutamine is the most abundant amino acid in the bloodstream. It is important in nucleotide synthesis, is anti-catabolic, has anti-oxidant properties via metabolism to glutathione, may enhance immune responsiveness and possesses immunoregulatory functions. Moreover, it reduces atrophy of intestinal mucosa in animals on total parenteral nutrition and prevents intestinal mucosal injury accompanying small bowel transplantation, chemotherapy and radiation. In the present study, we investigated the effects of glutamine on development of non-septic shock caused by zymosan. Mice received either zymosan (500 mg/kg, administered i.p., as a suspension in saline) or vehicle (saline). Glutamine (1.5 mg/kg i.p.) was administered 1 and 6 h after zymosan administration. Organ failure and systemic inflammation in mice were assessed 18 h after administration of zymosan and/or glutamine. Glutamine-treatment reduced the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan-injection and also attenuated the pancreatic and gut injury. Inflammatory and apoptotic parameters were evaluated to better investigate the effects of the glutamine-administration. So, by immunohistochemical analysis and in vitro assays, we have clearly showed that glutamine reduces: 1) the histological damage in pancreas and gut; 2) the inducible nitric oxide synthase expression; 3) nitrotyrosine and poly (ADP-ribose) formation; 4) TNF-α and IL-1β tissue and plasma levels; 5) FasL localization; and 6) alteration of the balance between Bax and Bcl-2. In addition, at the end of the observation period (7 days), zymosan causes severe illness in the mice characterized by a systemic toxicity, significant loss of body weight and mortality. Glutamine-treatment significantly reduced all these parameters.