Time course study of lipid peroxidation induced by N2-methyl-9-hydroxyellipticinium acetate or celiptium in rat renal cortex.
Celiptium is an ellipticine derivative with renal toxic side effects. It has recently been characterized as a lipid overload in proximal tubular cells where loss of total phospholipids (in particular phosphatidylethanolamine) and of polyunsaturated fatty acids are linked to the accumulation of unsaturated free fatty acids and aldehydes. A time course study of celiptium-induced peroxidative damage showed that a single dose of 40 mg/kg of celiptium induced no change in total or individual phospholipids of rat renal cortex. On the other hand, free fatty acids and thiobarbituric acid reactive substances increased as early as 1 hr after celiptium injection. 4-Hydroxynonenal (4-HNE) also increased whereas polyunsaturated fatty acids levels decreased at 6 and 24 hr. After 24 hr no change was detected in microsomal phospholipids. In contrast, the brush-border membranes showed alterations such as decrease in total phospholipids and polyunsaturated fatty acids levels accompanied by increase in aldehydes. It appears that peroxidative damage occurs in brush-border membranes of celiptium-treated rat kidneys with preferential losses of phosphatidylethanolamine (PE, 30%) and phosphatidylcholine (PC, 14%).
Thomas
N
N
Inserm Unité 295, UFR Médecine-Pharmacie, Rouen, France.
Raguenez-Viotte
G
G
Dieber-Rotheneder
M
M
Esterbauer
H
H
Fillastre
J P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004611:Ellipticines / Q000633:toxicity*; D005260:Female; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015227:Lipid Peroxidation; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000970:Antineoplastic Agents; D004611:Ellipticines; D010743:Phospholipids; C027767:elliptinium