DISTRIBUTION OF EPIDERMAL GROWTH-FACTOR IN THE KIDNEYS OF RATS EXPOSED TO AMIKACIN

The distribution of epidermal growth factor (EGF) was examined by immunocytochemistry in the kidneys of rats exposed to amikacin, an aminoglycoside antibiotic causing tubular necrosis at high dose. Five-animal groups were treated for 4 or 10 days with amikacin at daily doses of 15, 40, 80 or 200 mg/kg. The drug was delivered i.p. twice a day. One hour before termination, each rat received an i.p. injection of [H-3] thymidine to evaluate DNA synthesis in renal tissue. After sacrifice, the kidneys were processed for morphological (semithin and paraffin sections) and biochemical analysis (measurement of DNA synthesis by [H-3] thymidine incorporation in vivo). Amikacin induced in proximal tubules a dose-related lysosomal phospholipidosis, which was assessed by the morphometric evaluation of altered lysosomes ("myeloid bodies") on semithin section. However, frank evidence of acute tubular necrosis was only observed in rats receiving amikacin at a daily dose of 200 mg/kg. Concomitantly with the development of tubular necrosis, there was a rise in the rate of cell turnover, reflected by an increase of DNA synthesis in renal tissue. This sign of tubular regeneration was accompanied by a redistribution of EGF immunoreactivity, as revealed by immunocytochemical staining. Within renal cortex of control rats, EGF immunoreactivity predominantly appeared in distal tubules and collecting ducts (97% of examined tubular sections). In contrast, in treated animals where the renal cortex displayed evidence of tubular necrosis/regeneration, EGF immunoreactivity was frequently associated with proximal tubules (more than 30% of examined tubular sections, as compared to 3% in controls). This change in the topography of EGF immunoreactivity suggests that the growth factor might be involved in the process of tissue repair consecutive to drug-induced tubular necrosis.