Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis

Abstract

Sepsis leads to systemic hypotension, disturbed perfusion, in ammation and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and in ammatory processes, implicating a potential bene cial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 100 mg/kg) combination or NPW (0.1, 1 or 3 µg/kg) was given subcutaneously, and injections were repeated at 12th and 24th h.The sham-operated control group was treated with saline at the same time points. All rats were euthanized at the 25th h of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of Creactive protein, corticosterone and interleukin-6, while histopathologically veri ed tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to liver and lung was also suppressed by NPW. Although survival rate of the rats was not signi cantly prolonged by NPW, most of these improvements in systemic and local in ammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.

Neuropeptide W Facilitates Chronic Gastric Ulcer Healing by the Regulation of Cyclooxygenase and NF-κB Signaling Pathways

“…Accordingly, the agents that exert anti-in ammatory effects in acetic acid-induced gastric ulcer act by the inhibition of NF-κB (Konturek et al 2008). We have previously reported that NPW improved sepsis-induced multiple organ injury and stress-induced gastric injury by suppressing oxidative stress via the inhibition of NF-κB signaling (Atici et al 2022;Tamer et al 2022). In the present study, the serum or gastric proin ammatory cytokines TNF-α and IL-1β as well as the mRNA expression of NF-κB were reduced by NPW treatment in the rat gastric tissue, indicating the anti-in ammatory action of NPW against acetic acid-induced gastric injury also occurs through the suppression of NF-κB pathway.…”

“…Exogenously administered NPW modulates blood pressure and cardiovascular functions by its central as well as direct vascular effects (Ji et al 2015;Pate et al 2013;Yu et al 2007). Moreover, we have recently reported that peripherally administered NPW alleviates colonic in ammation, and protects against sepsis-induced oxidative multiorgan injury (Atici et al 2022) and stress-induced acute gastric ulcer (Arabacı Tamer et al 2023). However, the underlying mechanisms for the therapeutic action of NPW on the healing of gastric injury were not evaluated yet.…”

Thioredoxin-Interacting Protein (TXNIP) Knockdown Protects against Sepsis-Induced Brain Injury and Cognitive Decline in Mice by Suppressing Oxidative Stress and Neuroinflammation

“…Animals in the LPS group received an intraperitoneal injection (ip) of LPS (15 mg/kg) isolated from Escherichia coli O111:B4 and diluted in sterile normal saline, while the NC group received an equal volume of normal saline. Since LPS induced a high mortality rate, mice that died during the experiment (except for the survival study) were excluded and relevant mice were supplemented as previously described [ 29 – 31 ].…”

Myrtus communis L. Extract Ameliorates High Fat Diet Induced Kidney and Bladder Damage by Inhibiting Oxidative Stress and Inflammation

“…Scores were given as 0 -none, 1 -mild, 2 -moderate and 3 -severe for each criterion, using a semiquantitative scale as follows. In the renal tissue, (a) degeneration of glomerular structure and dilatation of Bowman's space, (b) degeneration of proximal and distal tubuli, (c) vascular congestion, interstitial edema and inflammatory cell infiltration; and in the urinary bladder (a) damage in urothelium, (b) inflammatory cell infiltration in mucosa, (c) inflammatory cell infiltration in mucosa and muscular layers (36,37). The maximum score was 9 for each tissue.…”