Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis

Abstract

Sepsis and septic shock are are among the major causes of mortality in intensive care units. The lung and kidney are the organs most affected by sepsis. Evidence exists that lipid peroxidation and apoptosis may be responsible for the high mortality due to sepsis. Ischemic preconditioning (IP) is a method for the protection of tissues and organs against ischemia/reperfusion injury by reducing reactive oxygen species levels, lipid peroxidation and apoptosis. In the present study, the effects of IP were investigated in cecal ligation and puncture (CLP)-induced sepsis in rats. The three groups of animals used in the present controlled study were the sham-operated group (sham, n=7), which only underwent a laparotomy; the sepsis group (sepsis, n=7), which underwent cecal ligation and perforation; and the IP + sepsis group (IP+sepsis, n=7), which underwent CLP immediately prior to the application of three cycles of IP to the hind limb. The study was terminated at 6 h after the induction of CLP. Blood, kidney and lung tissue samples were collected for the determination of serum creatinine, blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL) and lung tissue malondialdehyde (MDA) levels, as well as histological examination. The serum creatinine, plasma NGAL and lung tissue MDA levels in the sepsis group were significantly increased compared with those in the sham and the IP+sepsis groups (P<0.05). Alveolar macrophage counts, histological kidney and lung injury scores, kidney (caspase 3) and lung tissue immuonreactivity (M30) scores in the sepsis group were also significantly increased compared with those in the sham and IP+sepsis groups (P<0.05). The alveolar macrophage count in the IP+sepsis group was increased compared with that in the sham group (P<0.05). In conclusion, IP inhibits lipid peroxidation and attenuates histological injury and apoptosis in the lung and kidney during sepsis.

The Beneficial Effects of Agomelatine in Experimental Model of Sepsis Related Acute Kidney Injury

“…Olguner et al reported that an association between high kidney injury scores and sepsis has been histologically demonstrated. [28] For example, the histological kidney score was found to be higher in the sepsis group than in the sham group of a study by Koca et al These parameters were also used to evaluate an agent in AKI. [29] In the present study, histological findings were similarly used in the diagnosis stage, as well as to evaluate effects of agomelatine on AKI.…”

Adaptive response to hypoxia and remote ischaemia pre‐conditioning: a new hypoxia‐inducible factors era in clinical medicine

“…), and in sepsis‐induced organ damage (Olguner et al . ) and it has been suggested that this technique might be used for additional non‐ischaemic bowl disorders. The use of RIP in trauma may also improve the outcome of casualties, enhancing pre‐hospital and overall survival.…”

Subcellular Energetics and Metabolism: A Cross-Species Framework

“…HIF-1, which is protective in ischemia-reperfusion injury 88,217-220 and preconditioning, 19,20 exerts control over mitochondrial metabolism, 88 and appears to be upregulated in the setting of sepsis. 221 The complex link between HIF-1 and ROS/RNS (ROS stabilize HIF-1, 97-100 and ROS scavengers have been shown to destabilize HIF-1, 47,98,99,101 as described above) may explain why, despite some promising small pre-clinical trials, a phase III trial of NOS inhibition in humans with severe sepsis increased mortality in the treatment group. 222 Further strengthening the theory that hypoxia, HIF-1, and inflammatory disarray (e.g.…”