Ferulic acid prevents pathological and functional abnormalities of the kidney in Otsuka Long-Evans Tokushima Fatty diabetic rats.
We investigated the preventive effects of ferulic acid (FA) and alpha-tocopherol (AT) on the progression of diabetic nephropathy. Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as type 2 diabetes and non-diabetes models, respectively. Two-thirds of the OLETF rats were fed 0.2% FA-containing or 0.5% AT-containing chow. Diabetic nephropathy was assessed based on urinary protein excretion and pathological changes which were scored based on the percentages of extracellular matrix area in the glomerular area. Furthermore, renal messenger RNA (mRNA) expression of intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-beta1) was quantified by real-time polymerase chain reaction. After 12 weeks of FA- or AT-supplementation, urinary protein in untreated-OLETF group was significantly higher than that in LETO group, thus FA-supplementation significantly decreased urinary protein excretion. Pathological scores in FA-supplemented group were significantly lower than those in untreated OLETF group. Supplementation with either FA or AT significantly prevented the elevation of TGF-beta1 mRNA expression caused by diabetes. Treatment with neither FA nor AT had a significant effect on COX-2 or ICAM-1 mRNA expressions. We have demonstrated the preventative effects of FA on diabetic nephropathy via suppression of TGF-beta1 upregulation, furthermore FA may be more potent than AT.
Fujita
Atsuyo
A
The First Department of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama, PO 641-8509, Japan.
Sasaki
Hideyuki
H
Doi
Asako
A
Okamoto
Kunihisa
K
Matsuno
Shohei
S
Furuta
Hiroto
H
Nishi
Masahiro
M
Nakao
Taisei
T
Tsuno
Takuo
T
Taniguchi
Hisaji
H
Nanjo
Kishio
K
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003373:Coumaric Acids / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D016133:Polymerase Chain Reaction; D011507:Proteinuria; D051381:Rats; D011919:Rats, Inbred Strains; D020318:Rats, Long-Evans; D053773:Transforming Growth Factor beta1 / Q000235:genetics
D000975:Antioxidants; D003373:Coumaric Acids; D053773:Transforming Growth Factor beta1; C004999:ferulic acid