Association between remote organ injury and tissue polyamine homeostasis in acute experimental pancreatitis - Treatment with a polyamine analogue bismethylspermine

Experimental pancreatitis is associated with activation of polyamine catabolism. the polyamine analog bismethylspermine (me2spm) can ameliorate pancreatic injury.we investigated the roles of polyamine catabolism in remote organs during pancreatitis and explored the mechanism of polyamine catabolism by administering me2spm. acute pancreatitis was induced by an infusion of 2 or 6% taurodeoxycholate before me2spm administration. blood,urine and tissues were sampled at 24 and 72 h to assess multiorgan injury and polyamine catabolism. the effect of me2spm on mortality in experimental pancreatitis was tested separately. liver putrescine levels were elevated following liver injury. me2spm increased the activity of spermidine/spermine n1-acetyltransferase (ssat) and depleted the spermidine,spermine or putrescine levels. lung putrescine levels increased,and ssat and spermine decreased following lung injury.me 2spm enhanced the activity of ssat and decreased the spermidine and spermine levels. renal injury was manifested as an increase in creatinine or a decrease in urine output. decreases in kidney ssat,spermidine or spermine and an increase in putrescine were found during pancreatitis. in the 2% taurodeoxycholate model,me2spm decreased urine output and raised plasma creatinine levels. me2spm increased ssat and decreased polyamines. excessive me2spm accumulated in the kidney,and greater amounts were found in the 6%taurodeoxycholate model in which this mortality was not reduced by me2spm. in the 2% taurodeoxycholate model,me 2spm dose-dependently induced mortality at 72 h. like pancreatic injury,remote organ injury in pancreatitis is associated with increased putrescine levels. however,me2spm could not ameliorate multi-organ injury.me2spm administration was associated with significant renal toxicity and induced mortality,suggesting that the current dose is too high and needs to be modified. copyright © 2011 by institute of pharmacology polish academy of sciences.