PMID- 20403083
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20211020
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 114
IP  - 1
DP  - 2010 Jul
TI  - Mitochondrial protection after traumatic brain injury by scavenging lipid peroxyl 
      radicals.
PG  - 271-80
LID - 10.1111/j.1471-4159.2010.06749.x [doi]
AB  - Mitochondrial dysfunction after traumatic brain injury (TBI) is manifested by 
      increased levels of oxidative damage, loss of respiratory functions and 
      diminished ability to buffer cytosolic calcium. This study investigated the 
      detrimental effects of lipid peroxyl radicals (LOO(*)) and lipid peroxidation 
      (LP) in brain mitochondria after TBI by examining the protective effects of 
      U-83836E, a potent and selective scavenger of LOO(*) radicals. Male CF1 mice were 
      subjected to severe controlled cortical impact TBI (CCI-TBI) and treated with 
      either vehicle or U-83836E initiated i.v. at 15 min post-injury. Calcium (Ca(++)) 
      buffering capacity and respiratory function were measured in isolated cortical 
      mitochondrial samples taken from the ipsilateral hemisphere at 3 and 12 h 
      post-TBI, respectively. In vehicle-treated injured mice, the cortical 
      mitochondrial Ca(++) buffering capacity was reduced by 60% at 3 h post-injury (p 
      < 0.001) and the respiratory control ratio was decreased by 27% at 12 h post-TBI, 
      relative to sham, non-injured mice. U-83836E treatment significantly (p < 0.05) 
      preserved Ca(++) buffering capacity and attenuated the reduction in respiratory 
      control ratio values. Consistent with the functional effects of U-83836E being as 
      a result of an attenuation of mitochondrial oxidative damage, the compound 
      significantly (p < 0.001) reduced LP-generated 4-hydroxynonenal levels in both 
      cortical homogenates and mitochondria at both 3 and 12 h post-TBI. Unexpectedly, 
      U-83836E also reduced peroxynitrite-generated 3-nitrotyrosine in parallel with 
      the reduction in 4-hydroxynonenal. The results demonstrate that LOO(*) radicals 
      contribute to secondary brain mitochondrial dysfunction after TBI by propagating 
      LP and protein nitrative damage in cellular and mitochondrial membranes.
FAU - Mustafa, Ayman G
AU  - Mustafa AG
AD  - Spinal Cord & Brain Injury Research Center, University of Kentucky College of 
      Medicine, Lexington, Kentucky 40536-0509, USA.
FAU - Singh, Indrapal N
AU  - Singh IN
FAU - Wang, Juan
AU  - Wang J
FAU - Carrico, Kimberly M
AU  - Carrico KM
FAU - Hall, Edward D
AU  - Hall ED
LA  - eng
GR  - P01 NS058484/NS/NINDS NIH HHS/United States
GR  - P30 NS051220/NS/NINDS NIH HHS/United States
GR  - R01 NS046566/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20100416
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Chromans)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Free Radicals)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Piperazines)
RN  - 133681-84-2 (U 78517F)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain Injuries/*metabolism
MH  - Calcium/metabolism
MH  - Cell Respiration
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Chromans/chemistry/*pharmacology
MH  - Free Radical Scavengers/*pharmacology
MH  - Free Radicals/metabolism
MH  - Lipid Peroxidation/*drug effects
MH  - Male
MH  - Mice
MH  - Mitochondria/*drug effects/metabolism
MH  - Neuroprotective Agents/chemistry/*pharmacology
MH  - Oxidative Stress
MH  - Piperazines/chemistry/*pharmacology
MH  - Stereoisomerism
PMC - PMC3526891
MID - NIHMS428474
EDAT- 2010/04/21 06:00
MHDA- 2010/07/20 06:00
PMCR- 2012/12/20
CRDT- 2010/04/21 06:00
PHST- 2010/04/21 06:00 [entrez]
PHST- 2010/04/21 06:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
PHST- 2012/12/20 00:00 [pmc-release]
AID - JNC6749 [pii]
AID - 10.1111/j.1471-4159.2010.06749.x [doi]
PST - ppublish
SO  - J Neurochem. 2010 Jul;114(1):271-80. doi: 10.1111/j.1471-4159.2010.06749.x. Epub 
      2010 Apr 16.