Effects of probucol on renal function and urinary protein excretion in spontaneously hypercholesterolemic rats fed a normal or high cholesterol diet.
OBJECTIVE
Spontaneously hypercholesterolemic (SHC) rats develop hypercholesterolemia and focal glomerular sclerosis, and have been thought to be a model of lipid-induced glomerular injury. However, recent studies suggest that the hypercholesterolemia might be due to secondary mechanisms by massive proteinuria. The purpose of the present study was to determine in SHC rats the effects of a high cholesterol diet on serum lipid profiles and renal function/histology, and to examine whether or not the model of lipid-induced renal injury could be developed in a short period of the time. The effects of probucol were also studied.


METHODS
SHC rats were fed a high cholesterol diet for 6 weeks (H) or with probucol (HP), while control SHC rats were fed normal rat chow (N) or with probucol (P). Lipid profile and renal function/histology were examined.


RESULTS
H and HP showed increased levels of urinary protein excretion and serum creatinine, as well as extremely high serum cholesterol levels, compared with N and P. HP tended to show reduced urinary protein excretion compared with H, but the difference was not statistically significant. H and HP presented histologically characteristic changes with numerous foam cells accumulated in the glomerular mesangial area, and showed glomerular sclerosis.


CONCLUSIONS
The data demonstrate that SHC rats have an intrinsically abnormal lipid metabolism, and that probucol does not exert obviously beneficial effects on renal function or lipid-lowering action. A lipid-induced renal injury model of rats was produced in 6 weeks.
Nakao
Akihide
A
Department of Nephrology and Endocrinology, School of Medicine, University of Tokyo, Tokyo, Japan. akihide-tky@umin.ac.jp
Nosaka
Kazuo
K
Imaki
Hiromi
H
Noiri
Eisei
E
Toda
Akiko
A
Doi
Kento
K
Suzuki
Yoshifumi
Y
Fujita
Toshiro
T
Kimura
Satoshi
S
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D011341:Probucol / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D012720:Severity of Illness Index
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D011341:Probucol