Vitamin E treatment of experimental glomerular disease in rats.
BACKGROUND
Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary heart disease and it also inhibits the proliferation of VSMCs in vitro. Thus, we investigated the effect of vitamin E on glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two rat models of glomerular disease.


METHODS
A remnant kidney rat model accelerated with hyperlipidemia was used to examine progressive glomerular sclerosis leading to chronic renal failure. A rat model of MC-proliferative GN was induced by the intravenous administration of absorbed rabbit anti-rat thymocyte serum (ATS).


RESULTS
In the remnant kidney rat model, dietary supplementation with vitamin E (500 IU dl-alpha-tocopheryl acetate/kg) and cholesterol (2%) significantly inhibited glomerular sclerosis and macrophage infiltration in glomeruli relative to controls receiving basal and cholesterol-supplemented diets. In the ATS-induced GN model, glomerular cell proliferation (principally MCs) was lower in rats fed diets supplemented with vitamin E (1000 IU dl-alpha-tocopheryl acetate/kg) compared with controls fed the basal diet only. Although the degree of glomerular macrophage infiltration was similar in both groups, fewer proliferative cell nuclear antigen (PCNA)-positive cells were observed in the vitamin E group, suggesting that MC proliferation was suppressed via the inhibition of intracellular transduction.


CONCLUSIONS
Supplemental dietary vitamin E suppresses MC proliferation and glomerular sclerosis in models of glomerular disease in rats. This action of vitamin E in experimental nephritis suggests the value of clinical trials testing the potential benefit of vitamin E in chronic GN patients.
Third Department of Internal Medicine, Wakayama Medical College, Japan. hotani@wakayama-med.ac.jp
H
H
Otani
M
M
Mune
S
S
Yukawa
D
D
Smith
M
M
Meydani
J
J
Blumberg
D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D019587:Dietary Supplements; D005921:Glomerulonephritis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology*
D000961:Antilymphocyte Serum; D002791:Cholesterol, Dietary; D014810:Vitamin E