X-Message-Number: 22572
Date: Wed, 24 Sep 2003 17:23:20 -0700 (PDT)
From: Doug Skrecky <>
Subject: luteolin may eliminate renal cell injury during preservation

 Bioflavonoids attenate renal proximal tubular cell injury during cold
 preservation in Euro-Collins and University of Wisconsin solutions
 Kidney International Vol. 63 2003; 554-563

     Background. Cold ischemia and reperfusion during kidney
 transplantation are associated with release of free oxygen radicals and
 damage of renal tubular cells. Bioflavonoids may diminish cold
 storage-induced injury due to antioxidant and iron chelating activities.
 This study was designed to delineate the renoprotective mechanisms of
 bioflavonoids and to define the renoprotective mechanisms of
 bioflavonoids and to define the structural features conferring
 cytoprotection from cold injury.
     Methods. LLC-PK1 cells were preincubated for three hours with
 bioflavonoids and cold stored in University of Wisconsin (UW) or
 Euro-Collins (EC) solution for 20 hours. After rewarming, cell viability
 was assessed by the lactate dehydrogenase (LDH) release, MTT test and
 amino acid transport activity. Lipid peroxidation was assessed from the
 generation of thiobarbituric acid-reative substances.
     Results. Twenty hours of cold storage of LLC-PK1 cells resulted in a
 substantial loss of cell integrity that  was more pronounced in the EC
 (LDH  release, 93.6 +-1.6%) than the UW solution (67.2 +-6.9% ;P<0.0001).
 Pretreatment with quercetin significantly enhanced cell survival (LDH
 release, 5.4 +-2.7% for UW and 8.4 +-4.2% for EC) in a concentration
 dependant manner. Structure-activity studies  revealed similar
 renoprotection for kaempferol, luteolin and fisetin, unlike myricetin,
 morin, apigenin,  naringenin, catechin, silibinin and rutin. Lipid
 peroxidation was reduced (UW alone, 2.7 +-1.2 vs UW+quercetin 0.5 +-0.2
 nmol/mg protein, P<0.01), and threonine uptake completely sustained by
 pretreatment with quercetin, kaempferol, luteolin, and fisetin. However,
 renoprotection by fisetin was rapidly lost during rewarming. Protective
 properties of bioflavonoids were governed by the number and arrangement
 of hydroxyl substitutes, electron-delocalization, sterical planarity, and
 lipophilicity of the basic diphenylpyran skeleton.
     Conclusion. Cold storage-induced renal tubular cell injury is
 ameliorated by bioflavonoids. Renoprotective effects of bioflavonoids are
 defined by structure, suggesting that flavonoids are incorporated into
 membrane lipid bilayers and interfere with membrane lipid peroxidation.

 Further quote:
 "Complete inhibition of LDH release was obtained with 25 micromol/L
 luteolin in both preservation solutions. At this concentration metabolic
 activity was sustained almost completely in the UW solution
 (91.4 +-11.9%), but only partially in the EC solution (64.1 +-5.2%).
 Full  protection of metabolic activity in EC solution was achieved at
 300 micromol/L luteolin."

 Additional comments by poster:
     It might be worth looking to see what the effect of luteolin is on
 cryoprotectant toxicity, and whether vitrified organs can maintain
 viability after liquid nitrogen storage.
     There exists a possibility of slowing human aging with luteolin,
 since it is a good inhibitor of human SIRT1, is nontoxic, and has a
 fairly low molecular weight. (Small molecule activators of sirtuins
 extend Saccharomyces cerevisiae lifespan; Nature, epub August 24, 2003)
     One source of luteolin is rooibos tea. Age-associated deteriorative
 changes in the brains of 24 month old Wistar rats were completely
 suppressed, if they were fed rooibos tea in place of water. (Neuroscience
 Letters Vol.196 1995; 85-88)

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=22572