Gentamicin or chlorphentermine induction of phospholipidosis in the developing organism: role of tissue and species in manifestation of toxicity.
Daily, s.c. injection of gentamicin (100 mg/kg) for 2 days produced a significant increase in total phospholipid content of newborn rat kidney. Separation of individual phospholipid components revealed a significant rise in renal phosphatidylserine, phosphatidylinositol and phosphatidylcholine, whereas no marked change was noted in sphingomyelin, phosphatidylethanolamine or phosphatidylglycerol. Gentamicin did not significantly alter individual phospholipid classes and total phospholipid content in newborn rat liver and lung. Daily, oral chlorphentermine (60 mg/kg) administration also elevated total renal phospholipid levels and all individual phospholipid classes except sphingomyelin. In addition, a significant rise in all phospholipid components and total phospholipid content was noted in lungs of chlorphentermine-treated newborns. In the case of rat kidney, both gentamicin and chlorphentermine produced the greatest percentage of increase in phosphatidylinositol, whereas in lung phosphatidylcholine exhibited the highest percentage of elevation in response to chlorphentermine. In newborn rat liver, chlorphentermine did not induce alterations in individual and total phospholipid content. Gentamicin or chlorphentermine (1 mg/egg) failed to induce a phospholipidosis in chick embryo kidney and liver. Evidence suggests that drug-induced phospholipidosis is both species- and tissue-dependent and that this metabolic phenomenon is associated with inhibition of lysosomal phospholipases.
D000818:Animals; D000831:Animals, Newborn; D002745:Chlorphentermine / Q000633:toxicity*; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008064:Lipidoses / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D010645:Phentermine / Q000031:analogs & derivatives*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins; D010743:Phospholipids; D010645:Phentermine; D002745:Chlorphentermine