Profiles of serum proteins and free amino acids associated with chloroquine retinopathy

Abstract

ABSTRACT.Purpose: The effects of chronic chloroquine administration on serum proteins and free amino acids of rabbits and the accompanying ultrastructural changes in the retina were investigated. Methods: Thirty pigmented rabbits were injected intramuscularly with chloroquine diphosphate (14 mg/Kg bw). Fifteen rabbits served as control. Blood samples drawn after 1, 2, 3, 4, 5, 6 and 12 months were assayed for serum proteins by Bio-analytic kits and horizontal electrophoretic technique. Free amino acids were determined by Beckman analyzer. Central retinal tissue was fixed in 4% glutaraldehyde, embedded in araldite CY 212 and sectioned for ultrastructural examination. Results: Histopathologic changes were apparent within three months, initially affecting the pigment epithelium and photoreceptors and later involving the remaining neuroretinal layers. Hypoproteinemia gradually developed mainly due to a sharp drop in albumin and alpha 1 and 2 globulin fractions, inspite of an increase in beta and gamma globulin fractions. The concentration of non-essential amino acids varied considerably from a depletion of taurine, aspartine, glutamine, tryptophan and arginine to an increase of serine, alanine, GABA and ornithine. The most outstanding effect was the disappearance of tyrosine and its return to normal value at the end of the experiment. Conclusion: The disturbances in protein pattern and free amino acid levels are an indication of chloroquine toxicity and may be implicated in the retinopathy.

Effect of Chloroquine on Glucose Metabolism

“…This finding is supported by the finding that chloroquine inhibits protein biosynthesis in bovine [25] in rabbit retinal preparation [20,44] and in pancreatic islets and last but not least, the inhibition of the heme-dependent protein synthesis in malaria parasite [26]. Chloroquine was found to cause disturbance in serum proteins leading to hypoproteinemia and disturbance in free amino acid levels in rats [27].…”

“…The effect of cloroquine on glucose homeostasis has been studied by many scientists evoking controversy regarding the effet of the drug on insulin metabolism. Furthermore, our previous studies on the drug showed a disturbed lipid and amino acids metabolism [27,44]. Therefore, it seemed appropriate to study the effects of chloroquine (acute and chronic) on glucose homeostasis in a trial to resolve the controversy and to better understand the extent of its effects due to the importance of this drug in the treatment field.…”

“…Inhibition of hemedependent protein synthesis in malaria parasite [26] was observed. It has been also reported to cause disturbances in serum proteins and in free amino acids in rats [27]. Others demonstrated that chloroquine inhibits the liver cathepsin B which is the major protein proteolysis in liver [28], inhibits protein synthesis in yeast cell [29] and inhibits protein degradation in muscle as evidenced by an increase in muscle protein content [19].…”

Glutamate Uptake is Inhibited by Tamoxifen and Toremifene in Cultured Retinal Pigment Epithelial Cells

“…Chloroquine treatment has been found to affect the RPE and photoreceptor layer and to cause hypoproteinaemia and decrease in the serum glutamate levels (El‐Sayed et al 1998). Glutamate dehydrogenase activity and glutamate transport across the mitochondrial membrane have been shown to decrease due to choloroquine (Jarzyna et al 1997).…”

“…Chloroquine is used for the treatment of malaria and rheumatoid arthritis. One of its serious side effects is retinopathy (Bruinink et al 1991; El‐Sayed et al 1998). Tamoxifen and toremifene are antioestrogens that are widely used in breast cancer therapy.…”