[Alterations in phosphatidylcholine and phospholipase A2 of the renal tissue in gentamicin nephrotoxicity: comparative study with buthionine sulfoximine administered model].
We investigated to confirm the biochemical mechanisms of the hypothesis that lipid peroxidation participates in the pathogenesis of aminoglycoside-induced nephrotoxicity. Male Sprague-Dawley rats were injected with gentamicin (GM), 300mg/kg per day. Twenty-four hours after the injection the rats were killed and the renal cortex was processed for glutathione (GSH), malondialdehyde (MDA), phospholipase A2 (PLA2), phosphatidylcholine (PC), sphingomyelin (SPH) and phospholipids (PL). And we also studied the GSH reduced rats by buthionine sulfoximine (BSO) administration, to compare the biochemical differences with these parameters in two groups. GM induced a significant decrease of PLA2, SHP/PC ratio and GSH. Marked elevation of MDA (lipid peroxidation) and PC were observed after a single injection of GM. In contrast, BSO injected rats were not showed increment of tissue MDA, in spite of marked reduction of renal GSH. These data support the conclusion that accelerated lipid peroxidation occurs early in the course of GM administration and inhibition of lysosomal PLA2 activity involved in the degradation of lysosomal membrane which consisted of phospholipids.
Soejima
A
A
First Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Suzuki
M
M
Waku
M
M
Kitamoto
K
K
Nagasawa
T
T
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019328:Buthionine Sulfoximine; D004195:Disease Models, Animal; D005839:Gentamicins; D005978:Glutathione / Q000172:deficiency*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley
D005839:Gentamicins; D010713:Phosphatidylcholines; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D010741:Phospholipases A; D054467:Phospholipases A2; D005978:Glutathione