N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis

Abstract

The aim of the present study was to investigate the protective effects of N-acetylcysteine (NAC) on contrast-induced acute kidney injury in rats with unilateral hyronephrosis. Eighty-two male Sprague Dawley rats were randomized to undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68). After 3 weeks, the UUO animals were randomized to three groups: NAC gastric perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24); and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were injected with iohexol. One day after contrast, half of the rats were sacrificed to assess the pathological changes to the kidneys, serum creatinine, serum neutrophil gelatinase-associated lipocalin (NGAL), renal cell apoptosis rate and expression of apoptosis regulators Bcl-2/Bax. The remaining rats underwent obstruction relief and were analyzed 3 weeks later. Compared with the controls, serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3 weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum NGAL levels compared with UUO+iohexol rats (all P<0.05). Following modeling, UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular cells, higher expression of Bax mRNA, and lower ratio of Bcl-2/Bax (all P<0.05). Three weeks after obstruction relief, UUO+iohexol+NAC rats exhibited a lower apoptosis rate, lower Bax mRNA expression, higher expression of Bcl-2 mRNA and higher ratio of Bcl-2/Bax (all P<0.05) compared with day 1 following drug administration. The prophylactic use of NAC reduced the apoptotic rate of renal tubular cells following contrast exposition, which was accompanied by changes in the expression of Bcl-2/Bax mRNA.

Deleterious Effect of Urografin on the Renal Tubules of Adult Albino Rats and the Possible Protective Effect of N-Acetylcysteine Light and Electron Microscopic Study

“…In this work, after injection of Urografin, some tubules revealed destruction of the apical plasma membrane with obvious decrease of their height and displaying highly vacuolated cytoplasm with dark pyknotic nuclei. These results are in agreement with Kohli et al [23] and Xia et al [18] who reported similar results like destroyed microvilli, vacuolation of cytoplasm and renal tubular damage.…”

“…As a preventive tool from contrast-induced nephropathy, in the present work we tried to study N-Acetylcysteine protective effect and found that it decreased greatly most of the harmful effects of Urografin on the kidney tubules with apparent improvement in the histological renal picture. These results are in accordance with Xia et al [18] who stated that Acetylcysteine has apparently decreased apoptosis occurring in renal tubular cells of rats as a response to ureteric obstruction with CM , and ameliorates kidney injury.…”

“…In the present study, after Urografin injection, the principal findings were in the form of tubular dilatation, or severe tubular destruction with appearance of intratubular debris. These results coincide with Xia et al [18] who reported similar changes in the form of collapse of the lumen of kidney tubules, presence of protein and cellular casts in their lumen or severe renal interstitial fibrosis.…”

“…Group IV (UG + NAC group): consisted of 8 rats received N-Acetylcysteine (NAC) the same as group II. Then , Urografin was injected the same as in group III and NAC was administered again twice for the next 24 hours after Urografin injection [13,18] .…”

“…Rats of groups II and IV were given an equivalent dose of the human 70 kg adult dose 600 mg twice daily for 3 days by oral route before Urografin injection and for 24 hours after. The dose of Urografin and the oral Acetylcysteine was calculated as follows: Dosage = (M× Wr) / Wm where M= the amount of medication, Wr =weight of rat and Wm=weight of standard physiological man (70kg) [17,18] .…”