Reversal of experimental myoglobinuric acute renal failure with bioflavonoids from seeds of grape.
Rhabdomyolysis may account for about 10% of all cases of acute renal failure (ARF). This study was performed to explore the protective influence of proanthocyanidins from seeds of grape in an experimental model of myoglobinuric ARF. Rats were injected with 50% glycerol (8 mL/kg, im) followed immediately and daily in the next three days by ip proanthocyanidins (20 mg/kg) or saline. After 96 h rats were sacrificed and kidney morphology, kidney cortex peptidase activities, and malondialdehyde (MDA) content were determined. A moderate renal failure was produced by glycerol injection with blood urea of 31.8+/-11.0 vs. 7.68+/-0.24 m mol/L, and serum creatinine of 153. +/-38.2 vs. 39.6+/-9.0 micromol/L, in glycerol-induced ARF vs. control rats, respectively. Rats that received proanthocyanidins in addition to glycerol had significantly lower (p < 0.01) blood urea and serum creatinine levels compared to those receiving glycerol alone. These functional differences between the glycerol and glycerol plus proanthocianidins groups were also confirmed histologically. Kidney cortex dipeptidylpeptidase IV (DPP IV) activity was not significantly changed in glycerol-induced ARF, however, markedly increased after proanthocyanidins treatment. Kidney cortex malondialdehyde content was found significantly increased in glycerol-induced ARF over control level, and was markedly reduced by proanthocyanidin treatment. Taken together, these results provide strong evidence for the protective role of proanthocyanidins from seeds of grape in glycerol-induced ARF. The effect is probably due to the antioxidant activity of proanthocyanidins and to increased expression of kidney cortex DPP IV with effective degradation of TNF-alpha. This may provide therapeutic opportunities of preventing and/or treating myoglobinuric ARF in humans.
Stefanovic
V
V
Institute of Nephrology and Hemodialysis, University School of Medicine, Nis, Yugoslavia. stefanovic@cent.co.yu
Savic
V
V
Vlahovic
P
P
Cvetkovic
T
T
Najman
S
S
Mitic-Zlatkovic
M
M
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005419:Flavonoids / Q000008:administration & dosage; D005990:Glycerol; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism*; D009212:Myoglobinuria / Q000188:drug therapy / Q000517:prevention & control; D044945:Proanthocyanidins; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012206:Rhabdomyolysis / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D019685:Rosales
D000872:Anthocyanins; D000975:Antioxidants; D005419:Flavonoids; D044945:Proanthocyanidins; C013221:proanthocyanidin; D008315:Malondialdehyde; D005990:Glycerol