Adriamycin-induced focal glomerular sclerosis : Pathogenetic development and alteration of glomerular epithelial cells

Abstract

Pathogenesis of focal glomerular sclerosis was examined in adriamycin (AD)-induce nephrotic rats. Experimental animals were divided into two groups. Group I was induced with a single intraperitoneal injection of 6 mg/kg BW of AD. This group was sacrificed 1 and 3 days and 1, 2, 3 and 4 weeks after dosage, Group II was given dosages (3 mg/kg BW) four times at one week intervals, and sacrificed at 4, 6, 8, 12 and 18 weeks after the last injection. Glomeruli of 3 days to 3 weeks in group I showed minimal alterations but those of 4 weeks of group I and all the animals of group II showed focal glomerular sclerosis (FGS). The basic findings common to groups I and II by electron microscopy were glomerular epim thelial alterations, which were characterized by the foot processes, detachment from GBM, the presence of numerous intracytoplasmic vesicles and filaments (microfilament) of 5-6 nm in diameter. From the observation by immunof luorescent microscopy we suggested that the filaments in the epithelial cells were of actin. These actin filaments showed an increase in amount and unusual distribution in the altered epithelial cells. We suggest that an increase or abnormal distribution of actin filaments may lead to a deformation of the epithelial cells and their detachment from the glomerular basement membrane (GBM). This GBM then rapidly wrinkles, providing one of the causative factors of segmental sclerosis.