Recovery from Glycerol-Induced Acute Kidney Injury Is Accelerated by Suramin

Abstract

Acute kidney injury (AKI) is a common and potentially lifethreatening complication after ischemia/reperfusion and exposure to nephrotoxic agents. In this study, we examined the efficacy and mechanism(s) of suramin in promoting recovery from glycerol-induced AKI, a model of rhabdomyolysis-induced AKI. After intramuscular glycerol injection (10 ml of 50% glycerol per kilogram) into male Sprague-Dawley rats, serum creatinine maximally increased at 24 to 72 h and then decreased at 120 h. Creatinine clearance (CrCl) decreased 75% at 24 to 72 h and increased at 120 h. Suramin (1 mg/kg i.v.) administered 24 h after glycerol accelerated recovery of renal function as demonstrated by increased CrCl, decreased renal kidney injury molecule-1, and improved histopathology 72 h after glycerol injection. Suramin treatment decreased interleukin-1␤ (IL-1␤) mRNA, transforming growth factor-␤ 1 (TGF-␤ 1 ), phospho-p65 of nuclear factor-B (NF-B), and cleaved caspase-3 at 48 h compared with glycerol alone. Suramin treatment also decreased glycerol-induced activation of intracellular adhesion molecule-1 (ICAM-1) and leukocyte infiltration at 72 h. Urinary/ renal neutrophil gelatinase-associated lipocalin 2 (NGAL) levels, hemeoxygenase-1 expression, and renal cell proliferation were increased by suramin compared with glycerol alone at 72 h. Mechanistically, suramin decreases early glycerol-induced proinflammatory (IL-1␤ and NF-B) and growth inhibitory (TGF-␤ 1 ) mediators, resulting in the prevention of late downstream inflammatory effects (ICAM-1 and leukocyte infiltration) and increasing compensatory nephrogenic repair. These results support the hypothesis that delayed administration of suramin is effective in abrogating apoptosis, attenuating inflammation, and enhancing nephrogenic repair after glycerol-induced AKI.

Kinin B2receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis

“…Previous studies show [21] that renal TGF-β1 expression 48 h after im glycerol injection in mice is 1.5 times greater than our results indicate. It is important to note that the lineage of the animals used was different and that the endogenous gene studied was also different.…”

“…In mice, particularly male C57Bl/6 mice, the normal serum creatinine level (SCr) is approximately 0.8 ± 0.1 mg/dL [20] , which is similar to the values found in the control groups (Table 1). In a recent study [21] , the authors showed using the glycerol model in rats, that the peak of renal function impairment occurs between 48 and 72 h, as evidenced by SCr levels. In our study, we investigated the peak of injury.…”

“…Regarding the release of proinflammatory cytokines (e.g., IL-1β) and growth factors with a known profibrotic effect (TGF-β1), some authors [21] have shown that in the rat glycerol model, the mRNA expression levels of IL-1β peak 48 h after treatment, while in our work, the same expression levels were observed in GB2KO animals, whereas GWT animals showed expression levels similar to those found 24 h post-treatment by these authors. In our study, we found a strong negative association between the expression of B2R and IL-1β, which may indicate that B2R does not induce inflammation in the kidneys.…”

Antioxidant and Nephroprotective Activities of Aconitum heterophyllum Root in Glycerol Induced Acute Renal Failure in Rats

“…ARF was induced by intramuscular injection single doses of glycerol (10 ml/kg) into both the hind limbs in equal volume [33].…”

Diabetes-Induced Renal Injury in Rats Is Attenuated by Suramin

“…In this regard, delayed administration of suramin, a drug that has been used extensively in humans to treat trypanosomiasis, was recently shown to decrease renal injury in various animal models of acute kidney injury and renal inflammation and fibrosis in chronic kidney disease (Zhuang et al, 2009;Liu et al, 2011a;Korrapati et al, 2012). Because patients with DN usually have some degree of renal inflammation and fibrosis (Mathew et al, 2011;Najafian et al, 2011), it would be clinically useful if delayed administration of suramin prevents inflammation and fibrosis.…”