Abstract
Specific-pathogen-free (SPF) swine were given orally 15 mg/kg of chloroquine daily; 8 were sacrificed at 24 hours after 2-12 doses and 3 at 6, 10 and 16 days after completing 14 daily doses. Liver, myocardium and diaphragm and biceps femoris muscles were saved for ultrastructural evaluations and chloroquine assay procedures. The most consistent changes were found in lysosomes and related structures. After a transient decrease, evident only in the liver, lysosomal structures increased in number and size with the tissue concentrations of chloroquine. Lysosomes were aggregated and often contained incompletely digested substances and subsequently concentric membranous whorls or membranous cytoplasmic bodies (MCB). Since these changes were found at peak tissue concentrations, it was suggested that chloroquine or its metabolites were inhibiting the intracellular digestive system. "Ring structures," found only in muscle tissue, were thought to be Golgi membranes predestined for lysosomal formation. Dilation and proliferation of the terminal cisternae of the longitudinal sarcoplasmic reticulum in skeletal muscle were consistent ultrastructural changes associated with chloroquine toxicity in the pig. In general, concentrations of chloroquine increased in all four tissues with each day of treatment and declined with the length of time after cessation of treatment. Pigs with greater areas of pigmented skin has higher concentrations of chloroquine both initially and in the regression period than did lightly pigmented animals. The severity of the lysosomal changes in all tissues examined and of the sarcotubular changes in skeletal muscle was directly proportional to tissue concentrations of chloroquine. Changes were found to be reversible.
Sprowls, Robert Wayne (1974). Development and regression of cellular lesions induced by chloroquine in liver, skeletal muscles, and cardiac muscle of swine. Doctoral dissertation, Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -173266.