Effects of amifostine on glycerol-pretreated rabbit kidneys.
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 amifostine group compared to amifostine+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, amifostine 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 amifostine exerts its effects are not known.
Barun
Süreyya
S
Department of Pharmacology, Medical School, Gazi University, 06510 Beşevler, Ankara, Turkey. sbarun99@hotmail.com
Ertoy
Dilek
D
Dileköz
Ergin
E
Müftüoglu
Sevda
S
Erten
Yasemin
Y
Sucak
Gülsan
G
Bali
Musa
M
Tekeli
Nurçin
N
Sarioglu
Yusuf
Y
Ercan
Zeynep Sevim
ZS
D000109:Acetylcholine; D058186:Acute Kidney Injury / Q000139:chemically induced; D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005990:Glycerol; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010477:Perfusion; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents
D000975:Antioxidants; D014665:Vasodilator Agents; D004999:Amifostine; D000109:Acetylcholine; D005990:Glycerol