Effects of amifostine on glycerol-pretreated rabbit kidneys

BARUN S., ERTOY D., DILEKOZ E., Muftuoglu S. F., ERTEN Y., SUCAK G., ...More

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, vol.97, no.3, pp.168-173, 2005 (SCI-Expanded) identifier identifier identifier


Glycerol-induced acute renal failure is an experimental model for myoglobinuric nephropathy. Amifostine is a cytoprotective agent which scavenges the free radicals. Since there is enhanced production of reactive oxygen metabolites in glycerol-induced acute renal failure, we wanted to examine whether amifostine has a protective role against vascular reactivity and histological changes in kidneys isolated from glycerol-pretreated rabbits. Perfusion pressure was recorded from kidneys obtained from rabbits injected with glycerol 3 hr before the experiments and from glycerol-pretreated and non-pretreated rabbits injected with amifostine 30 min. before the experiments. Acetylcholine-induced (10(-8)-10(-5) M) vasodilatation was tested following the construction of submaximal vasoconstriction by phenylephrine. Histological investigation was performed using light microscope. Acetylcholine-induced vasodilatation was found to be significantly decreased in glycerol, glycerol+ amifostine and amifostine groups compared to controls at all concentrations. Reduction in acetylcholine-induced vasodilation was more prominent in arnifostine group compared to arnifostine +glycerol group. There was histological renal damage in all experimental groups and this damage was more pronounced in glycerol +amifostine group. In conclusion, contrary to expectation, arnifostine per se led to histological damage and potentiated the histological damage caused by glycerol and produced a decrease in acetylcholine-induced vasodilatation. The mechanisms by which arnifostine exerts its effects are not known.