Isoflurane Preconditioning Ameliorates Renal Ischemia-Reperfusion Injury through Antiinflammatory and Antiapoptotic Actions in Rats

Abstract

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury via inflammation and cell apoptosis. Volatile anesthetics have been shown to exert organ-protective effects against kidney damage in vivo and in vitro. In the present study, we investigated the effects of isoflurane, a commonly used volatile anesthetic, on renal I/R injury and the underlying mechanisms. Rats subjected to renal I/R displayed higher serum creatinine and blood urea nitrogen levels than sham rats as well as severe histopathological damage. Renal I/R also resulted in a nuclear factor-κB (NF-κB)-mediated inflammatory response and dysfunction of the p53-Bax-caspase-3 apoptotic pathway. Rats preconditioned with 1.5% isoflurane for 2 h had better renal function and less tubular apoptosis 24 h after I/R injury than control rats. Pretreatment with isoflurane suppressed renal NF-κB activation, leading to a reduction in proinflammatory molecules (high-mobility group box 1, interleukin-1β, and tumor necrosis factor-α) both in the kidneys and circulation. In addition, rats subjected to isoflurane preconditioning had a higher Bcl-2/Bax ratio and less cleaved caspase-3. Our findings suggest that preconditioning with a clinically relevant concentration of isoflurane attenuates renal I/R injury, based at least in part on its ability to modulate renal inflammation and apoptosis.Key words acute kidney injury; ischemia-reperfusion; volatile anesthetic; inflammation; apoptosis Renal ischemic-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), which occurs in many clinical settings including shock, renal transplantation, and renal artery angioplasty.1) Renal I/R injury always implies a poor prognosis and no effective therapy is currently available. Although the underlying mechanisms for renal I/R injury have been extensively studied, the pathophysiologic process involving inflammation and cell apoptosis and its relationship to subsequent renal injury remain to be fully elucidated.Nuclear factor-κB (NF-κB) is one of the most critical transcription factors involved in many inflammatory conditions, including renal I/R injury. Activation of NF-κB is a critical step in the systemic and renal inflammatory response, which leads to the release of proinflammatory cytokines including high-mobility group box 1 (HMGB1), 2) interleukin-1β (IL-1β), 3) and tumor necrosis factor-α (TNF-α).4) It has also been observed that the p53-Bax-caspase-3 apoptotic pathway is involved in renal I/R injury. 4,5) P53 can induce the downregulation of anti-apoptotic Bcl-2 and the upregulation of pro-apoptotic Bax. A decrease in the Bcl-2/Bax ratio triggers cytochrome c release from mitochondria, which results in the activation of caspase-3 and a chain reaction leading to apoptosis.6,7) Therefore, inhibiting the coexisting processes of inflammation and apoptosis provides a potential approach to the prevention and treatment of renal I/R injury.Isoflurane is a volatile anesthetic commonly used in clinical surgical settings. Previous studies have indicated ...

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Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy

“…With respect to endothelial cell integrity, contradicting findings 49,50 may reflect the tested preparation and dose and duration of isoflurane anesthesia. 52,53 Experiments in a TBI model in rats in which different anesthetic and sedative agents, including propofol and ketamine, were administered early after injury showed that rats treated with isoflurane had the best cognitive recovery and hippocampal neuronal survival. 51 In contrast, lower concentrations, as used here, have been reported to protect heart, kidney, and brain tissue from ischemic injury.…”

“…51 In contrast, lower concentrations, as used here, have been reported to protect heart, kidney, and brain tissue from ischemic injury. 52,53 Experiments in a TBI model in rats in which different anesthetic and sedative agents, including propofol and ketamine, were administered early after injury showed that rats treated with isoflurane had the best cognitive recovery and hippocampal neuronal survival. 54 Consistent with our results in the paraoxon model, isoflurane was reported to decrease BBB leakage in a rat stroke model 55 and subarachnoid hemorrhage.…”

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