Genistein attenuates renal fibrosis in streptozotocininduced diabetic rats.
Mol Med Rep
; 19(1): 423-431, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30431100
ABSTRACT
The present study aimed to investigate the antifibrogenic effects of genistein (GEN) on the kidney in streptozotocin (STZ)induced diabetic rats and to determine the associated mechanisms. Rats were randomized into four groups Normal control (N), STZ (S), L (STZ + lowdose GEN) and H (STZ + highdose GEN). After 8 weeks, the fasting blood glucose (FBG) level, the ratio of kidney weight to body weight (renal index), 24h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal total antioxidant capacity (TAOC), superoxide dismutase (SOD), lipid peroxidation (LPO), malondialdehyde (MDA) and hydroxyproline (Hyp) contents were measured. The histomorphology and ultrastructure of the kidney were also assessed. In addition, mRNA expression levels of transforming growth factorß1 (TGFß1) and protein expression levels of nuclear factor erythroid 2related factor 2 (Nrf2), heme oxygenase1 (HO1), NAD(P)Hquinone oxidoreductase 1 (NQO1), TGFß1, mothers against decapentaplegic homolog 3 (Smad3), phosphorylated (p)Smad3 and collagen IV were estimated. Compared with group N, the levels of FBG, renal index, 24h urine protein, BUN, SCr, LPO, MDA and Hyp were increased, whereas the levels of TAOC and SOD were decreased in group S. The structure of renal tissue was damaged, and the expression of Nrf2, HO1 and NQO1 were reduced, whereas the expression of TGFß1, Smad3, pSmad3 and collagen IV were increased in group S. Compared with group S, the aforementioned indices were improved in groups L and H. In conclusion, GEN exhibited renoprotective effects in diabetic rats and its mechanisms may be associated with the inhibition of oxidative stress by activating the Nrf2HO1/NQO1 pathway, and the alleviation of renal fibrosis by suppressing the TGFß1/Smad3 pathway.
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Base de datos:
MEDLINE
Asunto principal:
Fibrosis
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Estreptozocina
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Genisteína
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Diabetes Mellitus Experimental
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Enfermedades Renales
Idioma:
En
Revista:
Mol Med Rep
Año:
2019
Tipo del documento:
Article