Phosphodiesterase-5 inhibitors ameliorate structural kidney damage in a rat model of contrast-induced nephropathy. (September 2020)

• Record Type: Journal Article
• Authors: Iordache, Andrei Mihai; Buga, Ana Maria; Albulescu, Dana; Vasile, Ramona Constantina; Mitrut, Radu; Georgiadis, George; Zisis, Ioannis-Erineos; Mamoulakis, Charalampos; Tsatsakis, Aristidis; Docea, Anca Oana; Calina, Daniela
• Is Part Of: Food and chemical toxicology. Volume 143(2020)
• Publication Date: 2020-09
• Subjects: Acute kidney injury -- Contrast media -- Kidney -- Phosphodiesterase 5 inhibitors -- Sildenafil citrate -- Tadalafil; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111535
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: The aim of the study was to investigate the potential of sildenafil and tadalafil to ameliorate structural kidney damage in contrast-induced nephropathy (CIN). A rat model of CIN was developed by dehydration, administration of a nitric oxide inhibitor and a prostaglandin synthesis inhibitor (L-NAME/indomethacin) and contrast media exposure to iopromide. The effect of pre-treatment with sildenafil, tadalafil or N-acetyl cysteine (NAC) for 7 days prior to CIN induction was investigated. All animals were sacrificed at 24 h after CIN induction and both kidneys were collected. Histopathological examination was performed under light microscopy in serial tissue sections stained with hematoxylin and eosin. CIN group showed hydropic changes of the renal tubules (proximal and distal convoluted tubules and Henle's loop), an increased Bowman space with lobulated glomerulus and alteration of macula densa region of distal convolute tubules. The groups pretreated with sildenafil and tadalafil showed nearly normal histological aspects of renal tissue. The group pretreated with NAC showed similar but less intense histopathologic changes compared to CIN group. Sildenafil and tadalafil pre-treatment ameliorates CIN-related structural kidney damage and the protective potential of these agents is superior to NAC. Graphical abstract: Image 1 Highlights: Contrast-induced nephropathy is associated with structural kidney damage. Sildenafil and tadalafil reduce contrast-induced nephropathy risk. Sildenafil and tadalafil prevent hydropic changes of the renal tubules. Sildenafil and tadalafil prevent alteration of macula densa region of distal convolute tubes.