PMID- 18635243
OWN - NLM
STAT- MEDLINE
DCOM- 20081002
LR  - 20151119
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 231
IP  - 3
DP  - 2008 Sep 15
TI  - Cobalt chloride attenuates hypobaric hypoxia induced vascular leakage in rat 
      brain: molecular mechanisms of action of cobalt chloride.
PG  - 354-63
LID - 10.1016/j.taap.2008.05.008 [doi]
AB  - This study reports the efficacy of cobalt preconditioning in preventing hypobaric 
      hypoxia induced vascular leakage (an indicator of cerebral edema) using male 
      Sprague-Dawley rats as model system. Exposure of animals to hypobaric hypoxia led 
      to a significant increase in vascular leakage, reactive oxygen species (ROS), 
      nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels. There 
      was a marked increase in Nuclear Factor kappaB (NFkappaB) DNA binding activity 
      and levels of pro-inflammatory cytokines such as Monocyte chemoattractant protein 
      (MCP-1), Interferon-gamma (IFN-gamma), Interleukin-1 (IL-1), and Tumor Necrosis 
      Factor-alpha (TNF-alpha) and cell adhesion molecules such as Vascular Cell 
      Adhesion Molecule-1 (VCAM-1), and P-selectin. Chemical preconditioning by cobalt 
      for 7 days (12.5 mg Co/kg b.w., oral) significantly attenuated cerebral vascular 
      leakage and the expression of inflammatory mediators induced by hypoxia. 
      Administration of NFkappaB inhibitor, curcumin (50 mg/kg b.w.; i.p.) appreciably 
      inhibited hypoxia induced vascular leakage indicating the involvement of NFkappaB 
      in causing vascular leakage. Interestingly, cobalt when administered at 12.5 mg 
      Co/kg b.w. (i.p.), 1 h before hypoxia could not prevent the vascular leakage 
      indicating that cobalt per se did not have an effect on NFkappaB. The lower 
      levels of NFkappaB observed in the brains of cobalt administered animals might be 
      due to higher levels of antioxidant and anti-inflammatory proteins 
      (hemeoxygenase-1 and metallothionein). To conclude cobalt preconditioning 
      inhibited hypobaric hypoxia induced cerebral vascular leakage by lowering 
      NFkappaB DNA binding activity and its regulated pro-inflammatory mediators. This 
      is contemplated to be mediated by cobalt induced reduction in ROS/NO and increase 
      in HO-1 and MT.
FAU - Kalpana, S
AU  - Kalpana S
AD  - Experimental Biology Division, Defence Institute of Physiology and Allied 
      Sciences, Defence Research and Development Organisation, Lucknow Road, Timarpur, 
      Delhi-110054, India.
FAU - Dhananjay, S
AU  - Dhananjay S
FAU - Anju, B
AU  - Anju B
FAU - Lilly, G
AU  - Lilly G
FAU - Sai Ram, M
AU  - Sai Ram M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080520
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3G0H8C9362 (Cobalt)
RN  - EVS87XF13W (cobaltous chloride)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/metabolism/physiopathology
MH  - Brain Edema/chemically induced/metabolism/physiopathology
MH  - Capillary Leak Syndrome/chemically induced/*metabolism/*physiopathology
MH  - Capillary Permeability/drug effects/physiology
MH  - Cobalt/*toxicity
MH  - Hypoxia, Brain/chemically induced/*metabolism/*physiopathology
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
EDAT- 2008/07/19 09:00
MHDA- 2008/10/03 09:00
CRDT- 2008/07/19 09:00
PHST- 2007/10/08 00:00 [received]
PHST- 2008/04/12 00:00 [revised]
PHST- 2008/05/08 00:00 [accepted]
PHST- 2008/07/19 09:00 [pubmed]
PHST- 2008/10/03 09:00 [medline]
PHST- 2008/07/19 09:00 [entrez]
AID - S0041-008X(08)00217-2 [pii]
AID - 10.1016/j.taap.2008.05.008 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2008 Sep 15;231(3):354-63. doi: 
      10.1016/j.taap.2008.05.008. Epub 2008 May 20.