Effects of chronic chloroquine treatment on lysosomes of rat liver cells

Abstract

When single daily doses (40 mg/kg) of chloroquine were given to rats for 6 months, histochemical and ultrastructural investigations demonstrated a continuous process of autophagy by lysosomes, resulting in the formation of myeloid bodies and their extrusion into sinusoids and capillaries. Considerable acid phosphatase activity was observed in the rough endoplasmic reticulum, but not in the myeloid bodies. “Primary” lysosomes were rarely seen. There was single cell necrosis in the midzonal region of the liver lobule. Liver sections from rats sacrificed 3 months after drug treatment had been discontinued revealed no evidence of myeloid bodies, indicating that the drug effect is reversible. It is postulated that the mechanism of autophagy, consequent sequestration of damaged membranes, and their extrusion into extraparenchymal spaces may be an important factor in preventing liver damage. Our results also suggest that chloroquine acts primarily on lysosomal membranes.