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Identifier

000465640

Title

Η συμβολή των αναστολέων της φωσφοδιεστεράσης τύπου 5 (PDE-5I) στην πρόληψη της οξείας νεφρικής βλάβης μετά από παρενερική χορήγηση ιωδιούχων σκιαγραφικών ουσιών σε πειραματόζωα

Alternative Title

The contribution of phosphodiesterase type 5 inhibitors (PDE-5I) in the prevention of acute kidney injury after parenarenal administration of iodined contrast media in experimental animals

Author

Ζήσης, Ιωάννης-Ειρηναίος

Thesis advisor

Μαμουλάκης, Χαράλαμπος

Reviewer

Τσατσάκης, Αριστείδης
Τσιαούσης, Ιωάννης
Τόκας, Θεόδωρος
Στυλιανού, Κωνσταντίνος
Κεχαγιάς, Ηλίας
Λιαπάκης, Γεώργιος

Abstract

Contrast-induced nephropathy (CIN) is a potentially reversible form of acute kidney failure seen after administration of iodinated contrast media (CM) during imaging or interventional procedures. The incidence does not exceed 1% but in high-risk individuals the prevalence approaches 15% increasing morbidity, hospitalization time and mortality. The exact pathophysiology of CIN is not completely clear and available preventive measures are limited. CM exerts its nephrotoxic effects by several mechanisms, such as renal ischemia, release of oxygen free radicals, renal tubular epithelial cells damage, and reduction of NO production. Also, the hemodynamic changes created lead to hypoxia of the renal medulla through a reduction in blood flow. All patients to be administered CM should be assessed for the risk of developing CIN. Management of patients at risk remains supportive, relying primarily on intravenous hydration, either with saline or bicarbonate protocols since both show similar efficacy. Also, PDE5i, used as first-line treatment for erectile dysfunction in humans, appear to have promising nephroprotective effects as they show improvement in renal function/histopathological changes through various mechanisms, mainly by affecting hemodynamic changes, cell expression and mitochondrial response to oxidative stress and inflammation. Sildenafil and tadalafil have demonstrated their nephroprotective effect against CIN in animal models. Vardenafil has been evaluated in a limited number of studies, but none in a CIN model, while avanafil has never been previously studied in an AKI model. The aim of the present study is to assess for the first time the potential nephroprotective effects of vardenafil and avanafil in an animal CIN model. The study involved 25 male rats divided equally into 5 groups: control group, CIN group, CIN+NAC (100mg/kg/day) as positive control group, CIN+vardenafil (10mg/kg/day), CIN+avanafil (50mg/kg/ day). CIN was induced by dehydration, prostaglandin and nitric oxide synthesis inhibition as well as exposure to CM. Blood biochemical analysis was assessed at 24 and 48 h after CM exposure. At 48 hours after exposure and before sacrification, blood oxidative stress markers (GSH, CAT, TAC, TBARS, PROTC) were measured. Next, MMP-2, MMP-9, KIM-1, Cys-C, TAC, TBARS, PROTC were measured in kidney tissue, as well as histopathological findings. All treatment groups showed improvement in the histological lesions resulting from CM. sCr levels were decreased in all groups compared to the CIN group, as was also shown to be a significant decrease in MMP-2, MMP-9, Cys-C and KIM-1 compared to the CIN group. Finally, evaluating the results of oxidative stress markers, both in blood and in kidney tissue, improvement of the above was seen in all treatment groups. The above results support the nephroprotective effect of vardenafil and avanafil in an animal model of CIN, providing emerging evidence that these specific PDE5Is may prevent CIN.

Language

Greek, English

Subject

Αβαναφίλη

Αναστολείς φωσφοδιεστεράσης τύπου 5

Βαρδεναφίλη

Νεφροπάθεια

Νεφρός

Σκιαγραφικά μέσα

Issue date

2024-07-26

Collection