Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy

Abstract

Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR.

Autophagy-mediated neuroprotection induced by octreotide in an ex vivo model of early diabetic retinopathy

“…This positive effect of OCT on autophagy is coupled to the OCT well-known antiapoptotic actions, since our results demonstrate that the anti-apoptotic efficacy of OCT is completely abolished when the autophagic flux is blocked by CQ. Interestingly, OCT has been recently found to exert protective effects in the kidney after hepatic ischemia through induction of autophagy [61]. A wide variety of data support the notion that autophagy plays a fundamental role in preventing neurodegeneration [22,62,63], and perturbations of autophagy are thought to participate to the pathogenesis of all major neurodegenerative diseases [64,65].…”

Renoprotective effect of vildagliptin following hepatic ischemia/reperfusion injury

“…The model of renal injury after liver I/R injury was done as mentioned before in previous research [5,14] in which the liver I/R injury was first implemented. Briefly, rats in our experiment were anesthetized and subjected to a midline laparotomy under aseptic condition.…”

“…Prolonged liver ischemia followed by reperfusion stimulates the induction of pro-inflammatory cytokines as well as the reactive oxygen species (ROS) leading to hepatic cell as well as remote organ injury accompanied with high morbidity and mortality [3,4]. The injury induced by liver ischemia/reperfusion (I/R) in lung and kidney has been reported [5,6]. However, the exact mechanism underlying the renal injury induced by liver I/R has not been fully determined.…”

“…Till now, researchers are searching for suitable pharmacological interventions to minimize the kidney injury produced after hepatic I/R [5]. Dipeptidyl peptidase-4 (DPP-4) inhibitors, including linagliptin, sitagliptin, and vildagliptin (V), are class of hypoglycemic agents used for treating type II diabetes through inhibition of glucagon-like peptide-1 (GLP-1) degradation [7].…”

Understanding the inflammation-cancer transformation in the development of primary liver cancer

“…The PI3K/AKt/mTOR pathway is of great importance to the development, progression and treatment of HCC. It has been reported that TNF-α and IL-6 induced VEGF expression and angiogenesis can be significantly inhibited by rapamycin, indicating that mTOR plays an important role in inflammationinduced angiogenesis [50] . Inflammatory factors such as TNF-α, IL-6, IL-1β and other secretions are also regulated by mTOR signaling pathway [51] .…”