Salusin-alpha and salusin-beta are expressed in many tissues including the central nervous system, vessels and kidneys; they have been shown to decrease endoplasmic reticulum stress during heart ischemia/ reperfusion (I/R) and to decrease apoptosis. We investigated the relation of salusin-alpha and salusin-beta levels to acute ischemic renal failure. We also investigated whether these peptides are protective against renal I/R damage. Fifty-three rats were divided into six groups: control, I/R, I/R + salusin alpha 1, I/R + salusin-alpha 10, I/R + salusin-beta 1 and I/R + salusin-beta 10. After removing the right kidney, the left kidney was subjected to ischemia for 1 h and reperfusion for 23 h. The treatment groups were injected subcutaneously at the beginning of ischemia with 1 or 10 mu g/kg salusin-a, and1 or 10 mu g/kg salusin-beta. Histopathology was assessed at the end of the experiment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) activity and malondialdehyde (MDA) levels were measured in the kidney tissue. Serum levels of blood urea nitrogen (BUN), creatinine (Cre), tumor necrosis factoralpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) alsoweremeasured. Levels of salusina and salusin-beta were measured in the serum and kidney tissues of the control and I/R groups. SOD, CAT and GSH-PX activities were decreased and the levels of MDA, TNF-a, IL-6, IL-1 beta, BUNand Cre were increased in the I/R group compared to controls. Severe glomerular and tubular damage was apparent in the I/R group compared to controls. The level of salusin-alpha was decreased in the serum and kidney tissue of the I/R group compared to controls, whereas the level of salusin-a was decreased in the serum and increased in the kidney tissue. Salusin-a and salusin-beta administration increased SOD and GSH-PX enzyme activation and decreased the levels of MDA, TNF-a, IL-6 and IL-1 beta compared to the I/R group. BUN and Cre levels were decreased in the I/R + salusin-alpha 1 group and the level of Cre was decreased in I/R + salusin-beta 10 group compared to the I/R group. We demonstrated a protective effect of salusin-alpha and salusin-beta against renal I/R damage. Changes in the levels of salusin-alpha and salusin-beta in the I/R group suggest that these peptides may be associated with acute renal failure.