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.
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