The role of lysosomes in hyaline droplet nephropathy induced by a variety of pharmacological agents in the male rat.
The male rat is prone to hyaline droplet formation in renal proximal tubular cells. Several unrelated pharmaceutical agents exacerbate the formation and accumulation of these droplets. Where the loading of the proximal tubular cells is marked it gives rise to increased cell turnover and a hyaline droplet nephropathy develops. Cytochemical procedures, have confirmed that this accumulation of hyaline droplets represents an increase in the size and number of secondary lysosomes involved in protein uptake and metabolism. This predisposition of the male rat to develop hyaline droplet nephropathy relates to (1) the large amounts of the low-molecular-weight protein alpha 2U globulin in the glomerular filtrate, (2) the resistance of the globulin to proteolysis, and (3) the low protease activity in the proximal tubule lysosomes. The current data would suggest that the pharmacological agents, which cause the nephropathy, exert their effect by reducing the proteolytic breakdown of alpha 2U globulin in the proximal tubule lysosomes. This results in the overloading of a system which is already operating near maximal load. Female rats, and all other species excrete only small amounts of alpha 2U globulin or similar proteins, which are more easily hydrolyzed. Thus it is argued that the type of hyaline droplet nephropathy induced by these pharmacological agents is unique to the male rat and of little relevance to man.
Read
N G
NG
Department of Drug Safety Evaluation, Wellcome Research Laboratories, Wellcome Foundation Ltd., Beckenham, Kent, UK.
D000818:Animals; D006651:Histocytochemistry; D006838:Hydrocarbons / Q000633:toxicity; D007687:Kidney Tubules, Proximal / Q000737:chemistry; D008247:Lysosomes / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D009401:Nephrosis / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats
D006838:Hydrocarbons