Effect of the lipoprotein lipase activator NO-1886 on adriamycin-induced nephrotic syndrome in rats.
Hyperlipidemia associated with nephrotic syndrome may play a role in the deterioration of renal function. Tsutsumi et al have previously reported that the novel compound NO-1886 increases lipoprotein lipase (LPL) activity, resulting in a reduction of plasma triglycerides and an elevation of high-density lipoprotein (HDL) cholesterol in normal rats. The aim of this study was to ascertain whether NO-1886 suppresses the renal injury by treatment of the hyperlipidemia in an Adriamycin (Kyowa Hakko Kogyo, Tokyo, Japan) induced nephrosis rat model fed a high-protein diet that induced renal dysfunction and tubulointerstitial injury. Administration of Adriamycin caused hyperlipidemia, proteinuria, and edema with ascites in rats in 4 weeks. Furthermore, a combination of Adriamycin and a high-protein diet increased plasma creatinine and blood urea nitrogen (BUN) and decreased plasma albumin. Histologically, in Adriamycin-treated rats, marked interstitial cellular infiltration, tubular lumen dilation, and tubular cast formation in the kidney were observed. NO-1886 decreased plasma triglyceride and increased HDL cholesterol in Adriamycin-induced nephrotic rats. NO-1886 treatment reduced plasma creatinine and BUN levels and increased plasma albumin in Adriamycin-treated rats; it also ameliorated the ascites and proteinuria. Histologically, NO-1886-treated rats showed a quantitatively significant preservation of tubulointerstitial lesions. These data suggest that NO-1886 may have a protective effect against Adriamycin-induced nephrosis with tubulointerstitial nephritis in rats by a modification of the plasma lipid disorder.
Nakayama
K
K
First Department of Internal Medicine, Aichi Medical University, Japan.
Hara
T
T
Kusunoki
M
M
Tsutsumi
K
K
Minami
A
A
Okada
K
K
Sakamoto
S
S
Ohnaka
M
M
Miyata
T
T
Nakamura
T
T
Aoki
T
T
Fukatsu
A
A
Nakaya
Y
Y
Kakumu
S
S
D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D008076:Cholesterol, HDL / Q000097:blood; D004317:Doxorubicin / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000187:drug effects*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001549:Benzamides; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D008055:Lipids; D009943:Organophosphorus Compounds; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D004317:Doxorubicin; D008071:Lipoprotein Lipase