Abstract
New findings:
What is the central question of this study? The pathophysiology of remote hepatic injury following renal ischemia-reperfusion (IRI) is largely unknown. We aimed to investigate the role of circulating exosomes-miR-687 for remote hepatic injury. The study expected a modulatory impact of thymoquinone. What is the main finding and its importance? Exosomes-miR-687 were expressed in the renal IRI, circulated and deposited in the liver. Liver exosomes-miR-687 were correlated with liver inflammation and apoptosis Thymoquinone aborted the renal production of exosomes-miR-687 and its further circulation to the liver. Exosomes-miR-687 could be of significance in the pathogenesis of distant organ injury.
Abstract:
The pathophysiology of the remote hepatic injury following acute renal ischemia-reperfusion injury (IRI) raise a particular clinical interest. Secreted small non-coding microRNA (miRs) are thought to exist in exosome-encapsulated form. Thymoquinone (TQ) is the main bioactive ingredient of Nigella sativa. It presents several renoprotective actions. We expected relevance of the exosomes-miR-687 as it could act as a humoral mediator, and possible modulation by TQ. Thirty Adult male Wister albino rats were assigned into three groups (n = 10); 1) Sham-operated, 2) Renal ischemia-reperfusion (IRI), and 3) renal IRI pre-treated with TQ 10 mg.kg-1 .day-1 iv (TQ-IRI) for ten days in addition to a dose administered at the reperfusion onset. Following 24h of reperfusion, the IRI group showed renal tissue hypoxia-inducible factor upregulation (P<0.001). Electron microscopic images of exosomes and analysis of miR-687 revealed elevated levels, which were appeared in the circulation. Large amounts of exosomes-miR-687 were transmitted to the liver tissues. In the IRI group, liver transaminases (ALT, AST) were markedly (P<0.001) elevated. The hepatic tissue inflammatory markers (VCAM-1, MPO, MCP-1, and NF-κB) were upregulated (P<0.001) accompanied with elevated caspase-3. TQ suppressed (P<0.001) the renal expression and the release of exosomes-miR-687 to circulation and its further deposition in the liver tissue, consequently, TQ diminished (P<0.001) liver tissue inflammation and cellular apoptosis. Results were confirmed by histological tissue assessment.
In conclusion:
the exosomes-miR-687 liberated from injured renal tissues to the circulation may be an important factor in inducing remote hepatic injury. Exosomes-miR-687 inhibition by TQ protected both renal and hepatic tissues from injury. This article is protected by copyright. All rights reserved.
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