Glycerol induced ARF in rats is mediated by tumor necrosis factor-α

Abstract

Glycerol-induced acute renal failure (ARF) in rats is a model of acute trauma in which intra-muscular injection of 50% glycerol causes rapid myoglobinuria, oliguria, and a rapid reduction in glomerular filtration rate. We found that plasma tumor necrosis factor-alpha (TNF-α) is rapidly induced in glycerol injected rats. It can be detected in some animals as early as 30 minutes post-injection, peaks at one hour (range: 4 to 32 U/ml) with no significant difference between blood from renal vein and vena cava, and decreases by three hours. None was detected in control saline injected rats (P < 0.001). Four out of five rats infused with neutralizing anti-TNF-α antiserum (200 μl/300 g body wt) immediately prior to glycerol injection had significantly protected kidney function (P = 0.001). In these rats, plasma urea (104.8 ± 58.9 mg%) and creatinine (1.16 ± 0.38 mg%) were lower and creatinine clearance higher (0.34 ± 011 ml/min) than in glycerol injected animals pretreated with normal serum (291.8 ± 41.8 mg%, 3.15 ± 0.74 mg%, and 0.03 ± 0.03 ml/min, respectively) or animals injected with glycerol alone (302.6 ± 76.8 mg%, 3.45 ± 0.97 mg%, and 0.03 ± 0.03 ml/min, respectively). These results imply a direct role for TNF-α in pathogenesis of glycerol induced ARF in rats.