Mesna: a novel renoprotective antioxidant in ischaemic acute renal failure

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2001-03, Vol.16 (3), p.542-551
• Main Authors: Mashiach, Elisheva, Sela, Shifra, Weinstein, Talia, Cohen, Hector I., Shasha, Shaul M., Kristal, Batya
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - drug therapy; Acute Kidney Injury - pathology; Acute Kidney Injury - physiopathology; acute renal failure; Animals; antioxidant; Antioxidants - therapeutic use; Biological and medical sciences; Female; Free Radical Scavengers - therapeutic use; Glomerular Filtration Rate - drug effects; ischaemia–reperfusion; Ischemia - complications; Kidney - drug effects; Kidney - pathology; Medical sciences; mesna; Mesna - pharmacology; Mesna - therapeutic use; Microscopy, Electron; Natriuresis - drug effects; Oxidation-Reduction; Pharmacology. Drug treatments; Protective Agents - therapeutic use; Rats; Rats, Sprague-Dawley; reactive oxygen species; renal blood flow; Renal Circulation - drug effects; renal morphology; Sulfhydryl Compounds - metabolism; Urinary system
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/16.3.542

Background. Reactive oxygen species (ROS) play a key role in renal ischaemia–reperfusion injury. After establishing the in vitro anti‐oxidative potential of mesna, a sulfhydryl‐containing compound, its effect on kidney function and morphology in a rat model of ischaemic acute renal failure (ARF) was examined. Methods. Mesna (180 mg/kg) was administered at different time points relative to ischaemia and/or reperfusion onset. Kidney function was assessed by glomerular filtration rate (GFR) and fractional sodium excretion (FENa) before a 45‐min period of unilateral renal artery clamping and following 90 min of reperfusion. Mesna was administered by bolus, 30 min before the induction of ischaemia, 5 min before ischaemia, 5 min before reperfusion, and 5 min after the onset of reperfusion. Results. Mesna improved function of the ischaemic kidney at each administration. When mesna was administered 5 min before the onset of reperfusion, GFR reached 90–100% of its pre ischaemic value and FENa was improved by 75%. The beneficial effect of mesna was also demonstrated by light and electron microscopy. Kidneys treated with mesna 5 min before reperfusion resembled ischaemic non‐reperfused kidneys and showed subtle morphological and ultrastructural changes compared with ischaemic–reperfused kidneys. Mesna had no haemodynamic effect on renal blood flow and did not induce any osmotic diuresis. Conclusions. We suggest that mesna acts as an antioxidant. Its antioxidant potential together with optimal protection achieved when administered 5 min before reperfusion, supports the conclusion that mesna scavenges ROS generated at the onset of reperfusion, thus diminishing reperfusion injury and organ damage.