Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.
Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.
Szalay
László
L
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 Univ. Blvd., Volker Hall, Rm. G094, Birmingham, Alabama 35294-0019, USA.
Shimizu
Tomoharu
T
Suzuki
Takao
T
Yu
Huang-Ping
HP
Choudhry
Mashkoor A
MA
Schwacha
Martin G
MG
Rue
Loring W
LW
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*
D016207:Cytokines; D006360:Heat-Shock Proteins; D004958:Estradiol