X-Message-Number: 18625 Date: Fri, 22 Feb 2002 09:42:05 -0800 (PST) From: Doug Skrecky <> Subject: citrulline might reduce cryoprotectant toxicity <1 of 2> Title Cardioprotective effects of citrulline in ischemia/reperfusion injury via a non-nitric oxide-mediated mechanism. Source Methods & Findings in Experimental & Clinical Pharmacology. 22(7):563-71, 2000 Sep. Abstract The effects of L-citrulline, the byproduct of nitric oxide (NO) synthesis, and its stereoisomer D-citrulline were studied in a polymorphonuclear leukocyte (PMN)-dependent isolated perfused rat heart model consisting of 20 min of global ischemia and 45 min of reperfusion. Ischemic hearts reperfused with either D- or L-citrulline (20 nM) exhibited a marked preservation of left ventricular developed pressure and of maximal rate of development of left ventricular developed pressure, compared to hearts perfused without either D- or L-citrulline (both p < 0.001). In addition, both D- and L-citrulline significantly attenuated PMN accumulation in the post-reperfused myocardium from 288 +/- 33 PMNs/mm2 in untreated hearts to 89 +/- 10 and 76 +/- 6 PMNs/mm2, respectively (both p < 0.001). In isolated rat aortic rings, neither D- or L-citrulline induced any vasodilation or release of nitric oxide from the vascular endothelium. However, expression of P-selectin on the coronary vascular endothelium was markedly attenuated in hearts perfused with either D- or L-citrulline compared to ischemic-reperfused hearts without citrulline (both p < 0.001). These results provide evidence that D- or L-citrulline significantly attenuates PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart subjected to ischemia/reperfusion via a non-NO-mediated mechanism. <2 of 2> Citrulline, a novel compatible solute in drought-tolerant wild watermelon leaves, is an efficient hydroxyl radical scavenger FEBS Letters 508: 438-442 2001 Abstract: Drought-tolerant wild watermelon accumulates high levels of citrulline in the leaves in response to drought conditions. In this work, the hydroxyl radical-scavenging activity of citrulline was investigated in vitro. The second-order rate constant for the reaction between citrulline and hydroxyl radicals was found to be 3,900,000,000 M-1 s-1, demonstrating that citrulline is one of the most efficient scavengers among compatible solutes examined so far. Moreover, citrulline effectively protected DNA and an enzyme from oxidative injuries. Liquid chromatography-mass spectrometry analysis revealed that at least four major products were formed by the reaction between citrulline and hydroxyl radicals. Activities of metabolic enzymes were not inhibited by up to 600 mM citrulline, indicating that citrulline does not interfere with cellular metabolism. We reasoned, from these results, that citrulline contributes to oxidative stress tolerance under drought conditions as a novel hydroxyl radical scavenger. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=18625