Induction and exacerbation of hyaline droplet formation in the proximal tubular cells of the kidneys from male rats receiving a variety of pharmacological agents.
Kidneys from male and female Wistar rats dosed with 1 of 3 chemically unrelated pharmacological agents, a pyrazoline BW540C, a naphthoquinone BW58C and the levoisomer of tetramisole, levamisole or the light hydrocarbon Decalin, were examined by light and electron microscopy. Paraffin histology showed that all 4 agents induced and exacerbated hyaline droplet accumulation in the renal proximal tubular cells of the male rats. Resin histology at both the light and electron microscope level, along with cytochemical procedures for acid phosphatase and the protein 'alpha 2U globulin', helped further in the characterisation of these cytoplasmic inclusions. These techniques confirmed that the accumulation of hyaline droplets seen by paraffin histology represented an increase in the size and number of secondary lysosomes which have been shown to be involved in protein uptake and metabolism. Time course studies showed that increased numbers of small dense lysosomes appear first, which then increase in size, presumably by fusion. Crystalloid bodies form in these large lysosomes eventually giving rise to rectilinear bodies. The accumulation of these protein laden secondary lysosomes took place primarily in the cells of the S1 and S2 segments of the proximal tubules. In extreme cases of lysosomal accumulation however, loading of the S3 segments was noted. In tubules where cellular inclusion loading was heavy, there was evidence of increased cell turnover. The kidneys of female rats dosed with any one of the 4 agents appeared normal.
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Department of Drug Safety Evaluation, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Astbury
P J
PJ
Morgan
R J
RJ
Parsons
D N
DN
Port
C J
CJ
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000962:Antimalarials / Q000633:toxicity*; D005260:Female; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D007978:Levamisole / Q000633:toxicity*; D008297:Male; D009281:Naphthalenes / Q000633:toxicity; D009285:Naphthoquinones / Q000633:toxicity*; D011720:Pyrazoles / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000962:Antimalarials; D009281:Naphthalenes; D009285:Naphthoquinones; D011720:Pyrazoles; D007978:Levamisole; C046216:BW 540C; C007229:decalin; C045010:BW 58C