phytoestrogens and Fibrosis

In the last two decades, much controversy has grown over the use of soybean products in aquafeeds, especially for carnivorous fish like sturgeons. One point of discussion is the effect of soybean phytoestrogens on fish health. There are many aspects of phytoestrogen utilization in aquafeeds, therefore, the aim of this study is to verify if common legume phytoestrogens can affect juvenile cultured sturgeon erythrocyte and hepatocyte genotoxicity and cause liver pathology. Russian sturgeons were fed from 100 till 365 dph

Topics: Animals; Coumestrol; Diet; Estrogens, Non-Steroidal; Fibrosis; Genistein; Glycine max; Phytoestrogens; Water Pollutants, Chemical

Estrogen receptor β (ERβ) is the major ER subtype in hepatic stellate cells (HSCs). Previously we reported phytoestrogen calycosin suppressed liver fibrosis progression and inhibited HSC-T6 cell functions, suggesting the effects may be related to ERβ. Here, we explore the effect of overexpressed ERβ on human HSCs and the role of ERβ in pharmacological action of calycosin.. LX-2 cells were transfected with lentivirus to overexpress ERβ. In the presence or absence of overexpressed ERβ, the effects of ERβ and calycosin on proliferation, migration, activation, collagen production and degradation of TGF-β1-induced LX-2 cells and the role of ERβ in the inhibition effect of calycosin were investigated. LX-2 cells overexpressed with ERβ or treated with ER non-selective antagonist ICI182,780 were used to investigate the regulation of ERβ on JAK2/STAT3 signaling pathway. CCK-8 method was used to screen effective doses of calycosin and investigate cell proliferation. The cell migration was detected by transwell chamber assay. The expression of α-SMA was detected by immunofluorescence and western blot. The protein expressions of Col-I, MMP1, TIMP1, JAK2, p-JAK2, STAT3 and p-STAT3 were detected by western blot.. ERβ overexpressed lentivirus was successfully transfected into LX-2 cells with high efficiency. Overexpressed ERβ or calycosin alone inhibited the TGF-β1-induced LX-2 cell proliferation and migration, downregulated the protein expressions of α-SMA, Col-I, TIMP-1, p-STAT3 and upregulated MMP-1. Both overexpressed ERβ and calycosin had no significant effect on JAK2, p-JAK2 and STAT3 expressions. ERβ overexpression further enhanced the above effects of calycosin. However, after the cells were treated with ICI182,780, downregulation of STAT3 phosphorylation induced by calycosin was reversed.. ERβ mediated the inhibition of major functions of LX-2 cell possibly by inhibiting the phosphorylation of STAT3, and was an important pathway through which calycosin exerted anti-liver fibrosis effect.

Topics: Cell Proliferation; Estrogen Receptor beta; Fibrosis; Hepatic Stellate Cells; Humans; Isoflavones; Liver Cirrhosis; Matrix Metalloproteinase 1; Phosphorylation; Phytoestrogens; STAT3 Transcription Factor; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1

The aim of the present study was to investigate the effects of genistein (GEN) on myocardial fibrosis in type 1 diabetic rats and explore the underlying mechanisms. Rats were divided into 4 groups: Normal control (N), diabetic control (D), low‑dose GEN treatment (L) and high‑dose GEN treatment (H) groups. Following 8 weeks, the ventricular hemodynamic parameters, fasting blood glucose (FBG), heart‑weight to body‑weight ratio (HW/BW), myocardial hydroxyproline (Hyp) content, serum creatine kinase MB isozyme (CK‑MB), lactate dehydrogenase (LDH), tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6) levels were measured. The histomorphology and ultrastructure of the heart were observed. The protein expression of myocardial transforming growth factor‑β1 (TGF‑β1), mothers against decapentaplegic homolog (Smad)‑3, phosphorylated (p)‑Smad3, Smad4, collagen‑I and collagen‑III were estimated. Compared with the N group, while the cardiac function was decreased, the levels of FBG, HW/BW, Hyp content, CK‑MB, LDH, TNF‑α, IL‑1β and IL‑6 were increased in the D group. The myocardial histomorphological alterations and ultrastructure were damaged, and the protein expression of myocardial TGF‑β1, Smad3, p‑Smad3, Smad4, collagen‑I and collagen‑III were increased in the D group. Compared with the D group, there were no differences in the ventricular hemodynamic parameters, FBG and p‑Smad3 expression in the L group, while HW/BW, Hyp content, CK‑MB, LDH, TNF‑α, IL‑1β and IL‑6 levels were decreased. The myocardial histomorphological damage was alleviated and the protein expression of TGF‑β1, Smad3, Smad4, collagen‑I and collagen‑III was decreased in the L group. Compared with L group, excluding FBG, the aforementioned indices were improved in the H group. In conclusion, GEN can attenuate myocardial fibrosis in type 1 diabetic rats, and the underlying mechanisms may be associated with the reduction of CK‑MB and LDH leakage, inhibition of the inflammatory reaction, and suppression of the TGF‑β1/Smad3 signaling pathway to regulate collagen expression.

Topics: Animals; Cardiomyopathies; Collagen Type I; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Fibrosis; Genistein; Heart; Hemodynamics; Male; Myocardium; Phytoestrogens; Rats; Rats, Sprague-Dawley; Smad3 Protein; Smad4 Protein; Transforming Growth Factor beta1

Oxidative stress is a major cause of cardiovascular tissue fibrosis. We evaluated the effects of daily doses of soy isoflavones, genistein and daidzein on cardiovascular tissue fibrosis in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats and Long-Evans Tokushima Otsuka (LETO) non-diabetic rats as a severe or mild oxidative stress model, respectively. Glucose and lipid metabolisms did not improve with genistein or daidzein treatment. However, genistein decreased hydroxyproline concentrations in the heart. Hydroxyproline reductions as a result of genistein were mildly stronger than those of daidzein. Thus, genistein significantly suppressed the progression of myocardial fibrosis in LETO rats despite the insignificant changes in OLETF rats. Although a daily dosage of isoflavone was not sufficient to prevent tissue fibrosis under marked oxidative stress in the early stage of diabetes, isoflavones might promise significant clinical benefits by reducing oxidative stress in the heart during aging.

Topics: Analysis of Variance; Animals; Aorta, Thoracic; Blood Glucose; Blood Pressure; Cardiovascular System; Collagen; Disease Models, Animal; Disease Progression; Fibrosis; Heart Rate; Hydroxyproline; Isoflavones; Lipid Metabolism; Male; Myocardium; Organ Size; Oxidative Stress; Phytoestrogens; Rats; Rats, Inbred OLETF; Rats, Long-Evans; Severity of Illness Index; Soy Foods