Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy

Abstract

BackgroundContrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury.MethodsTwenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates.ResultsUrinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3μg/mmol versus 533.6μg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups.ConclusionsAscorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.

Magnetic resonance diffusion tensor imaging applied to rat model of contrast-induced acute kidney injury

“…A relation between faltering and tissue fibrosis has actually been demonstrated in a prior rat model of diabetic nephropathy ( Hueper et al, 2012 ). According to another study by Rollins et al (2017) declines in FA likely stem from necrosis/apoptosis of medullary tubular epithelial cells, impairing water diffusion along tubular structures. Cheung et al (2010) have further acknowledged reduced renal medullary FA values 5 h after ischemia-reperfusion injury, accompanied by cellular edema and histologic evidence of necrosis.…”

Potential role of Vitamin C intracoronary administration in preventing cardiac injury after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction

“…Recently, Rollins et al . [22] in a murine model of CI-AKI observed that ascorbic acid reduced the urinary NGAL-to-creatinine ratio, which is indicative of the frequency and severity of the renal injury.…”

Berberine alleviates contrast‐induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway

“…With the advancement of clinical treatment for CIN, drugs such as N‐acetylcysteine (NAC), 7 vitamin C 8 and statins 9 have been utilized. However, there is no strong evidence to prove that any drug can reduce the occurrence of CIN.…”