Protective effects of salusin-α and salusin-β on renal ischemia/reperfusion damage and their levels in ischemic acute renal failure

Biotech Histochem. 2017;92(2):122-133. doi: 10.1080/10520295.2017.1283056. Epub 2017 Mar 6.

Abstract

Salusin-α and salusin-β 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-α and salusin-β 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-α1, I/R + salusin-α10, I/R + salusin-β1 and I/R + salusin-β10. 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 μg/kg salusin-α, and 1 or 10 μg/kg salusin-β. 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 factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) also were measured. Levels of salusin-α and salusin-β 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-α, IL-6, IL-1β, BUN and 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-β was decreased in the serum and kidney tissue of the I/R group compared to controls, whereas the level of salusin-α was decreased in the serum and increased in the kidney tissue. Salusin-α and salusin-β administration increased SOD and GSH-PX enzyme activation and decreased the levels of MDA, TNF-α, IL-6 and IL-1β compared to the I/R group. BUN and Cre levels were decreased in the I/R + salusin-α1 group and the level of Cre was decreased in I/R + salusin-β10 group compared to the I/R group. We demonstrated a protective effect of salusin-α and salusin-β against renal I/R damage. Changes in the levels of salusin-α and salusin-β in the I/R group suggest that these peptides may be associated with acute renal failure.

Keywords: ischemia; kidney; reperfusion; salusin-α; salusin-β.

MeSH terms

  • Acute Kidney Injury / metabolism*
  • Animals
  • Apoptosis / physiology
  • Creatinine / metabolism
  • Glutathione Peroxidase / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kidney / metabolism*
  • Male
  • Malondialdehyde / pharmacology
  • Oxidative Stress / physiology
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology

Substances

  • Intercellular Signaling Peptides and Proteins
  • salusin-beta, rat
  • Malondialdehyde
  • Creatinine
  • Glutathione Peroxidase