Aged kidneys are refractory to ischemic postconditioning in a rat model

Abstract

Background: Ischemic postconditioning (IPoC) is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion that mechanically alters the hydrodynamics of reperfusion and it attenuates renal damage after ischemia/reperfusion (I/R) injury in vivo. But all of these data had been obtained in adult populations and whether this protection was maintained in aging kidneys was unknown. The objective of this study was to establish whether the efficacy of IPoC is maintained in aging kidneys. Materials and methods: The aged (24-monthold) and young (3-month-old) Wistar rats were used. Rats were subjected to 45 min of renal ischemia, both with and without treatment with IPoC. Serum urea nitrogen and creatinine levels, histological examination and apoptosis were assessed at 24 h. Oxidative stress was evaluated and apoptosis-related molecules were studied by Western blotting. Results: In young rat kidneys, IPoC significantly attenuated the renal dysfunction and cell apoptosis induced by I/R. In contrast, IPoC failed to limit renal dysfunction, possibly a consequence of increased apoptosis in aged rat kidneys. Conclusions: Our data indicated that IPoC was ineffective in aged rat kidneys. These findings may have major implications in that severe apoptosis in aged kidneys might be refractory to anti-apoptotic effect by IPoC.

Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury

“…Previously, a similar loss of protective effects in old animals was reported when attempted to apply ischemic pre- and postconditioning to aged kidneys and hearts [ 25 , 26 , 39 , 40 ]. Such loss of effectiveness can partly be explained by the fact that during aging tissue accumulate various age-dependent alterations affecting the functioning of organs [ 41 ].…”

“…However, the effectiveness of these elaborated approaches should be tested both in young and old animals, since approaches that have been shown to be efficient in young organisms, not always retained their protective effects in the elderly [ 24 ]. In particular, ischemic pre- and postconditioning, demonstrating a significant reduction of the severity of ischemic injury in the renal tissue of young animals, had no effect in old animals [ 25 , 26 ].…”

Hind limb perconditioning renoprotection by modulation of inflammatory cytokines after renal ischemia/reperfusion

“…The present findings are consistent with those of other studies, which revealed that ischemic conditioning inhibits the effects I/R in functional and morphological impairment of ischemic injured kidney. 12 There are experimental and clinical studies demonstrating the potent necrosis size-reducing effect of RPER in the myocardium or liver.…”

Aged kidney: can we protect it? Autophagy, mitochondria and mechanisms of ischemic preconditioning

“…As aging evidently affects mitochondria, a reasonable question arises as to whether mitochondriatargeted approaches can protect the aging kidney. Two works attempting to extend the protective effects of IPC and ischemic postconditioning to older animals yielded a disappointing result: these interventions were not protective in the kidney of old rats [18,154]. In one of these studies, aging was accompanied by an increase in the level of acetylation of the nuclei in the epithelial cells of the proximal tubules and a lack of growth in the number of lysosomes one day after I/R.…”