Renoprotective Effect of Vardenafil and Avanafil in Contrast-Induced Nephropathy: Emerging Evidence from an Animal Model

Abstract

The potential renoprotective effects of vardenafil (VAR) have been evaluated in a very limited number of studies using acute kidney injury animal models other than contrast-induced nephropathy (CIN) with promising results, while avanafil (AVA) has not been evaluated in this respect before. The purpose of this study was to evaluate for the first time the potential renoprotective effect of VAR and AVA in a rat model of CIN. Twenty-five male Wistar rats were equally assigned into five groups: control, CIN, CIN+N-acetyl cysteine (NAC) (100 mg/kg/day) as a positive control, CIN+VAR (10 mg/kg/day) and CIN+AVA (50 mg/kg/day). CIN was induced by dehydration, inhibition of prostaglandin and nitric oxide synthesis as well as exposure to the contrast medium (CM). Serum Cr (sCr) levels were measured at 24 and 48 h after CIN induction. At 48 h of CM exposure, animals were sacrificed. Matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, kidney injury molecule 1 (KIM-1) and cystatin-C (Cys-C) were measured on renal tissue. Histopathological findings were evaluated on kidney tissue. All treatment groups had close to normal kidney appearance. sCr levels subsided in all treatment groups compared to CIN group at 48 h following CIN induction. A significant decline in the levels of MMP-2, MMP-9, KIM-1 and Cys-C compared to CIN group was observed. These results provide emerging evidence that VAR and AVA may have the potential to prevent CIN.

Effects of Thymoquinone Nanoparticles on Paracetamol-Induced Nephrotoxicity by Mitigating Oxidative Stress and Inflammation in Rats

“…As earlier informed, PAR administration can trigger nephrotoxicity characterized by the eminent serum CYC, BUN and creatinine levels (Vasaikar et al, 2018;Alanezi et al, 2022;Topal et al, 2023). Our data shows that the TQNP significantly attenuated these elevations of BUN, CYC and creatinine in PAR-administered rats as synchronized with other previous works using taxifolin (Alanezi et al, 2022;Topal et al, 2023), vardenafil (Zisis et al, 2022), and trehalose (Hozhabri et al, 2022).…”

“…Of late, the hepatoprotective effects of TQNP on hepatotoxicity-triggered hepatic damage have been previously demonstrated (El-Far et al, 2021;Harakeh et al, 2022). Promising outcomes on the renoprotective ability of TQNP have been described in a restricted number of drug-triggered renal toxicity animal models (Zisis et al, 2022). The present study aimed to assess the potential renoprotective abilities of TQNP in a PAR-triggered nephrotoxicity rat model for the first time.…”

“…Renal impairment is among the serious adverse effects of PAR (Hussein et al, 2022;Fadil et al, 2023;Topal et al, 2023) and the clinical aspects of its persuaded acute renal damage (Focak and Suljevic, 2023;Topal et al, 2023). High oxidative stress (OS) markers and inflammatory mediators trigger cell death by inducing apoptosis or inflammation paths, which is powerfully interrelated with PAR-induced renal failure (Zisis et al, 2022). Therefore, decreasing OS and inflammation could be a potent safeguard against PAR-instigated renal failure.…”

“…Nowadays, natural molecules with powerful antioxidant and inflammatory abilities have received significant attention due to their protective roles against organ injury in numerous syndromes. However, these compounds' low absorption and inferior bioavailability and efficacy might hinder their clinical use (Zisis et al, 2022;Topal et al, 2023). More advanced, the phytochemical nano-encapsulation could improve its oral bioavailability and make it more effective, safe and applicable for targeting many diseases (Ahmed et al, 2021).…”

Resveratrol and lycopene ameliorate contrast-induced nephropathy in a rabbit model

“…15 Novel biomarkers 16,17 and agents with antioxidant and vasodilatory properties are attracting attention due to their ability to reduce oxidative stress/regulate vascular tone. 3,4,[18][19][20] The potential renoprotective effects of several antioxidants have been evaluated but none of them has been proven effective in human studies. 15 Resveratrol (Res) and lycopene (Lyc) are strong natural antioxidants with antimicrobial/anti-inflammatory activity found in red grapes/tomatoes.…”