Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta

Sci Rep. 2020 Mar 19;10(1):5040. doi: 10.1038/s41598-020-61268-9.

Abstract

Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-β1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-β1 as an attractive target for manipulation in this context.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / prevention & control
  • Animals
  • Aorta, Abdominal / surgery*
  • Aortic Aneurysm, Abdominal / surgery*
  • Constriction
  • DNA Damage
  • Ischemic Preconditioning / methods*
  • Male
  • Myocardial Reperfusion Injury / etiology*
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / prevention & control
  • NADPH Oxidases / metabolism
  • Rats, Wistar
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / prevention & control
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Surgical Procedures / adverse effects*
  • Vascular Surgical Procedures / methods

Substances

  • Transforming Growth Factor beta1
  • NADPH Oxidases