COMPARISON OF IN VIVO AND IN VITRO EFFECTS OF CHLOROQUINE ON HEPATIC LYSOSOMES

The acute effects of chloroquine on rat hepatic lysosomes were evaluated both in vivo and in vitro with the isolated perfused rat liver, liver slices, homogenates and large granule fractions. Lysosomal alterations were measured by analyses of the free and total hydrolytic activities of acid β-glycerophosphatase and β-glucuronidase in either liver homogenates or large granule fractions. Chloroquine administered intraperitoneally (i.p.) to 300 ± 20 g rats at doses of 1, 5, 10, 15 and 25 mg elicited moderate to marked lysosomal hydrolase alterations as manifest by increased free enzyme activities. A study of the time course of the hepatic lysosomal response to 10 mg chloroquine i.p. revealed labilization at 30, 60, 120 and 240 min, but a return to control values was observed at 24 hr post-injection. Chloroquine also induced lysosomal labilization in the perfused rat liver and liver slices. However, no hydrolase alterations were observed in liver homogenates or large granule fractions exposed to chloroquine. In accord with other studies employing intact cellular preparations, it is suggested that chloroquine is also a potent labilizer of cellular hepatic lysosomes. © 1969.