Glycerol induced ARF in rats is mediated by tumor necrosis factor-alpha.
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-alpha) 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-alpha antiserum (200 microliters/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-alpha in pathogenesis of glycerol induced ARF in rats.
Shulman
L M
LM
Nephrology Department, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Yuhas
Y
Y
Frolkis
I
I
Gavendo
S
S
Knecht
A
A
Eliahou
H E
HE
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control; D000818:Animals; D005990:Glycerol / Q000494:pharmacology*; D007106:Immune Sera / Q000276:immunology; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; D005990:Glycerol