Thermotolerance attenuates ischemia-reperfusion induced renal injury and increased expression of ICAM-1.
Thermotolerance describes the process in which hyperthermia induces a transient resistance of the stressed cells to subsequent episodes of oxidative stress. The aims of this study were first, to assess the effect of ischemia-reperfusion (IR) injury on renal function and the expression of the ICAM-1 receptor and MHC antigens, and second, to evaluate the protective effects of thermotolerance on IR induced renal injury and its potential for decreasing allograft rejection, by decreasing alloantigen expression. Sprague-Dawley rats were randomized into three groups: control, IR, and hyperthermia + IR (HIR) (n=8 per group). Thermotolerance was induced 18 hr prior to IR by increasing the core body temperature to 41 degrees C+/-0.5 degrees C for 15 min. After left uninephrectomy, IR was induced by clamping the right renal pedicle for 45 min, followed by 2 hr reperfusion. Myeloperoxidase (MPO) activity was used as an indicator of renal neutrophil influx. Kidney edema was assessed using the weight difference between left and right kidneys. Renal function was evaluated by measuring serum creatinine and urea 2 hr following clamp removal. Immunocytochemistry was used to measure expression of ICAM-1 and MHC antigen. Renal function was significantly impaired by IR with serum creatinine and urea levels of 131.5+/-5.01 microM and 11.2+/-0.71 mM, respectively, compared with controls of 67.9+/-5.11 microM and 8.1+/-0.36 mM, P<0.005 in both cases. Renal function was preserved in the HIR group, serum creatinine (84.8+/-8.58 microM) and urea (9.0+/-0.52 mM) were comparable to that of controls. Renal endothelium was activated in the IR group compared with controls, with increased ICAM-1, and tubular epithelium showed increased class II MHC expression. This up-regulation was prevented by prior induction of thermotolerance. Endothelial permeability was increased in the IR group with MPO activity of 0.8+/-0.08 units/g tissue--twice that of control levels P<0.05--and a marked increase in organ edema. Thermotolerance preserved endothelial barrier function. Thermotolerance may prevent IR injury by preventing endothelium activation and has the potential to modify allograft rejection by decreasing expression of ICAM-1, an important T cell receptor, and class II MHC.
Stokes
K Y
KY
The Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin.
Abdih
H K
HK
Kelly
C J
CJ
Redmond
H P
HP
Bouchier-Hayes
D J
DJ
D000064:Acclimatization / Q000502:physiology*; D000818:Animals; D002463:Cell Membrane Permeability / Q000528:radiation effects; D003404:Creatinine / Q000097:blood; D006649:Histocompatibility Antigens / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006358:Hot Temperature; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007668:Kidney / Q000098:blood supply*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D014508:Urea / Q000097:blood
D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; D014508:Urea; D003404:Creatinine