Relationship between glutathione content and formation of organic solvent-soluble fluorescent pigments in mice treated with chloroquine.
We examined the relationship between the amount of organic solvent-soluble fluorescent pigments (OFP), which are generally regarded as the products of lipid peroxidation, and the content of glutathione in chloroquine-treated mice in order to assess the toxicological significance of the formation of these fluorescent pigments. OFP extracted with chloroform/methanol (2:1, v/v) were quantified spectrophotofluorometrically (excitation, 380 nm; emission, 460 nm). The administration of chloroquine diphosphate (50 mg/kg, i.p.) greatly increased the fluorescent intensity of OFP in the kidneys, but not in the livers, whereas administration of this drug significantly decreased glutathione content in the livers. In contrast, depletion of glutathione, induced either by starvation or by pretreatment with buthionine sulfoximine, a potent inhibitor of glutathione synthesis, markedly augmented the fluorescence intensity of OFP in the livers of mice treated with chloroquine. In the serum of mice treated with chloroquine, the alteration in activity of acid phosphatase and gamma-glutamyl transpeptidase approximately paralleled changes in the formation of fluorescent pigments in the tissues. These findings suggest that glutathione is an important endogenous substance which influences the insult of chloroquine.
Nakagawa
K
K
Department of Food Science, Kyoto Women's University, Japan.
D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity; D019328:Buthionine Sulfoximine; D002738:Chloroquine / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D010860:Pigments, Biological / Q000032:analysis / Q000096:biosynthesis*; D013053:Spectrophotometry; D013217:Starvation; D005723:gamma-Glutamyltransferase / Q000097:blood
D000963:Antimetabolites; D010860:Pigments, Biological; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D002738:Chloroquine; D005723:gamma-Glutamyltransferase; D000135:Acid Phosphatase; D005978:Glutathione