Sodium arsenite induces heat shock protein-72 kilodalton expression in the lungs and protects rats against sepsis.
OBJECTIVE
To examine the hypothesis that induction of heat shock proteins by a nonthermal mechanism would confer protection against experimental sepsis.


METHODS
Prospective, blind, randomized, laboratory study.


METHODS
University research laboratory.


METHODS
Sixty-two adult male Sprague-Dawley rats (weight range 250 to 350 g).


METHODS
Administration of sodium arsenite or saline in an animal model of sepsis by cecal ligation and perforation.


RESULTS
Sixty-two rats were randomly divided into two groups: group 1 received sodium arsenite (6 mg/kg iv) and group 2 received saline injection, in a blinded fashion. Eighteen hours after receiving sodium arsenite or saline, cecal ligation and perforation were performed and the animals were monitored for mortality for 96 hrs. Sodium arsenite injection, in the absence of an increase in body temperature, induced heat shock protein of 72-kilodalton molecular weight expression in the lung, which was detected 2 hrs after injection, peaked between 9 and 24 hrs, and returned to baseline by 48 hrs. Prior administration of sodium arsenite conferred significant protection against cecal ligation and perforation-induced mortality at 18 hrs (p = .002) and 24 hrs (p v .026) after cecal ligation and perforation, and correlated with expression of heat shock proteins in the lungs. However, at 48 and 96 hrs, when heat shock protein expression returned to basal values, the mortality rates of both groups were indistinguishable.


CONCLUSIONS
We conclude that in vivo injection of sodium arsenite induces expression of HSP-72 in the lungs, and confers transient protection against experimental sepsis during the period that heat shock proteins are also expressed.
Ribeiro
S P
SP
Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Villar
J
J
Downey
G P
GP
Edelson
J D
JD
Slutsky
A S
AS
D000818:Animals; D018053:Arsenites / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism / Q000517:prevention & control*; D017670:Sodium Compounds / Q000008:administration & dosage*; D013997:Time Factors
D018053:Arsenites; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; C017947:sodium arsenite