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.

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