Protective effect of syringaresinol on rats with diabetic nephropathy via regulation of Nrf2/HO-1 and TGF- β1/Smads pathways

Purpose: To investigate the protective role of syringaresinol in a rat model of diabetic nephropathy (DN). Methods: Streptozotocin was injected intraperitoneally into rats to establish the diabetic model. Streptozotocin-induced rats were orally administered syringaresinol, and pathological changes in kidneys were assessed using hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine kidney injury indicators, 24-h urine proteins, blood urea nitrogen (BUN), and serum creatinine (SCR). Blood glucose was measured using a blood glucose meter, while levels of malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in kidney were also measured using ELISA. Results: Pathological changes in the kidneys were observed in rats post-streptozotocin treatment. Administration of syringaresinol reduced the lesion degree, with improved pathological morphology in kidney. Syringaresinol administration significantly attenuated streptozotocin-increased levels of BUN, SCR, 24-h urine protein, and blood glucose (p < 0.01). Streptozotocin-induced oxidative stress, shown by enhanced MDA level and reduced levels of SOD, CAT, and GSH-PX, was reversed in rat kidneys following syringaresinol administration. However, the expression levels of nuclear factor erythropoietin- 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins decreased, while transforming growth factor-beta 1 (TGF-β1) and signal transducer and transcriptional modulator (Smad) 2/3/7 proteins increased in rats post-streptozotocin treatment. Syringaresinol administration reversed the effects of streptozotocin on protein expression of Nrf2, HO-1, TGF-β1, and Smad 2/3/7. Conclusion: Syringaresinol exerted a protective effect against DN through activation of Nrf2 and inactivation of TGF-β1/Smad pathways. Thus, the compound can potentially be developed for management of diabetic nephropathy.

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Notoginsenoside R1 Protects db/db Mice against Diabetic Nephropathy via Upregulation of Nrf2-Mediated HO-1 Expression

Molecules ◽

10.3390/molecules24020247 ◽

2019 ◽

Vol 24 (2) ◽

pp. 247 ◽

Cited By ~ 10

Author(s):

Bin Zhang ◽

Xuelian Zhang ◽

Chenyang Zhang ◽

Qiang Shen ◽

Guibo Sun ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Panax Notoginseng ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Neuroprotective Effects ◽

Nitrogen Levels

Diabetic nephropathy (DN) is a leading cause of end-stage renal failure, and no effective treatment is available. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng, and our previous studies showed the cardioprotective and neuroprotective effects of NGR1. However, its role in protecting against DN remains unexplored. Herein, we established an experimental model in db/db mice and HK-2 cells exposed to advanced glycation end products (AGEs). The in vivo investigation showed that NGR1 treatment increased serum lipid, β2-microglobulin, serum creatinine, and blood urea nitrogen levels of db/db mice. NGR1 attenuated histological abnormalities of kidney, as evidenced by reducing the glomerular volume and fibrosis in diabetic kidneys. In vitro, NGR1 treatment was further found to decrease AGE-induced mitochondria injury, limit an increase in reactive oxygen species (ROS), and reduce apoptosis in HK-2 cells. Mechanistically, NGR1 promoted nucleus nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions to eliminate ROS that induced apoptosis and transforming growth factor beta (TGF-β) signaling. In summary, these observations demonstrate that NGR1 exerts renoprotective effects against DN through the inhibition of apoptosis and renal fibrosis caused by oxidative stress. NGR1 might be a potential therapeutic medicine for the treatment of DN.

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Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats

Cellular Physiology and Biochemistry ◽

10.1159/000489445 ◽

2018 ◽

Vol 46 (5) ◽

pp. 2056-2071 ◽

Cited By ~ 3

Author(s):

Long Zheng ◽

Long Li ◽

Guisheng Qi ◽

Mushuang Hu ◽

Chao Hu ◽

...

Keyword(s):

Growth Factor ◽

Protective Effect ◽

Renal Fibrosis ◽

Transforming Growth Factor ◽

Kidney Tissue ◽

Collagen I ◽

Enzyme Linked Immunosorbent Assay ◽

Mrna Levels ◽

Mesenchymal Transition ◽

Tgf Β1

Background/Aims: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. Methods: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days. The degree of renal damage and fibrosis was determined using histological assessment. The expression of collagen I, fibronectin, epithelial-mesenchymal transition markers, and Smad2/3 phosphorylation was examined by western blot analyses. Real-time PCR and enzyme-linked immunosorbent assay were performed in vivo to detect the levels of transforming growth factor (TGF)-β1 and various growth factors. Results: Telocytes attenuated renal fibrosis, as evidenced by reduced interstitial collagen accumulation, decreased expression of fibronectin and collagen I, upregulation of E-cadherin, and downregulation of α-smooth muscle actin. Furthermore, telocytes decreased serum TGF-β1 levels, suppressed Smad2/3 phosphorylation, and increased the expression of hepatocyte growth factor (HGF) in rat kidney tissue following UUO. Blockage of HGF counteracted the protective effect of telocytes on UUO-treated kidneys. Through the detection of HGF mRNA levels in vitro, we found that telocytes had no effect on HGF expression compared with renal fibroblasts. Conclusion: Telocytes attenuated UUO-induced renal fibrosis in rats, likely through enhancing the expression of HGF in an indirect manner.

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KIOM-79, an Inhibitor of AGEs–Protein Cross-linking, Prevents Progression of Nephropathy in Zucker Diabetic Fatty Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep078 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Young Sook Kim ◽

Junghyun Kim ◽

Chan-Sik Kim ◽

Eun Jin Sohn ◽

Yun Mi Lee ◽

...

Keyword(s):

Blood Glucose ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Cross Linking ◽

Kidney Weight ◽

Zucker Diabetic Fatty Rats ◽

Protein Cross Linking

Advanced glycation end products (AGEs) have been implicated in the development of diabetic complications, including diabetic nephropathy. KIOM-79, an 80% ethanolic extract obtained from parched Puerariae Radix, gingered Magnolia Cortex, Glycyrrhiza Radix and Euphorbia Radix, was investigated for its effects on the development of renal disease in Zucker diabetic fatty rats, an animal model of type 2 diabetes.In vitroinhibitory effect of KIOM-79 on AGEs cross-linking was examined by enzyme-linked immunosorbent assay (ELISA). KIOM-79 (50 mg/kg/day) was given to Zucker diabetic fatty rats for 13 weeks. Body and kidney weight, blood glucose, glycated hemoglobin, urinary albumin and creatinine excretions were monitored. Kidney histopathology, collagen accumulation, fibrinogen and transforming growth factor-beta 1 (TGF-β1) expression were also examined. KIOM-79 reduced blood glucose, kidney weight, histologic renal damage and albuminuria in Zucker diabetic fatty rats. KIOM-79 prevented glomerulosclerosis, tubular degeneration, collagen deposition and podocyte apoptosis. In the renal cortex, TGF-β1, fibronectin mRNA and protein were significantly reduced by KIOM-79 treatment. KIOM-79 reduces AGEs accumulationin vivo, AGE–protein cross-linking and protein oxidation. KIOM-79 could be beneficial in preventing the progression of diabetic glomerularsclerosis in type 2 diabetic rats by attenuating AGEs deposition in the glomeruli.

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Lovastatin Inhibits Transforming Growth Factor-β1 Expression in Diabetic Rat Glomeruli and Cultured Rat Mesangial Cells

Journal of the American Society of Nephrology ◽

10.1681/asn.v11180 ◽

2000 ◽

Vol 11 (1) ◽

pp. 80-87

Author(s):

SUNG IL KIM ◽

DONG CHEOL HAN ◽

HI BAHL LEE

Keyword(s):

Diabetic Nephropathy ◽

Blood Glucose ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Diabetic Rats ◽

Kidney Weight ◽

Urine Albumin Excretion ◽

Urine Albumin ◽

Ecm Proteins ◽

Tgf Β1

Abstract. Diabetic nephropathy is a leading cause of end-stage renal disease and is characterized by excessive deposition of extracellular matrix (ECM) proteins in the glomeruli. Transforming growth factor-β (TGF-β) is the major mediator of excessive accumulation of ECM proteins in diabetic nephropathy through upregulation of genes encoding ECM proteins as well as downregulation of genes for ECM-degrading enzymes. It has been shown that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, delays the onset and progression of different models of experimental nephropathy. To evaluate the effect of lovastatin on the development and progression of diabetic nephropathy, streptozotocin-induced diabetic rats were studied for 12 mo. In untreated diabetic rats, there were significant increases in blood glucose, urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression in the glomeruli compared with normal control rats treated with citrate buffer only. Treatment with lovastatin in diabetic rats significantly suppressed the increase in urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression despite high blood glucose levels. To elucidate the mechanisms of the renal effects of lovastatin, rat mesangial cells were cultured under control (5.5 mM) or high (30 mM) glucose with lovastatin alone, mevalonate alone, or with both. Under high glucose, TGF-β1 and fibronectin mRNA and proteins were upregulated. These high glucose-induced changes were suppressed by lovastatin (10 μM) and nearly completely restored by mevalonate (100 μM). These results suggest that lovastatin has a direct cellular effect independent of a cholesterol-lowering effect and delays the onset and progression of diabetic nephropathy, at least in part, through suppression of glomerular expression of TGF-β1.

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The Cell-Permeable Derivative of the Immunoregulatory Metabolite Itaconate, 4-Octyl Itaconate, Is Anti-Fibrotic in Systemic Sclerosis

Cells ◽

10.3390/cells10082053 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2053

Author(s):

John Henderson ◽

Sharadha Dayalan Naidu ◽

Albena T. Dinkova-Kostova ◽

Stefan Przyborski ◽

Richard Stratton ◽

...

Keyword(s):

Gene Expression ◽

Systemic Sclerosis ◽

Transforming Growth Factor Beta ◽

Target Genes ◽

Transforming Growth Factor ◽

Dermal Fibroblasts ◽

Heme Oxygenase 1 ◽

Quinone Oxidoreductase ◽

Tgf Β1

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that leads to skin fibrosis. Altered metabolism has recently been described in autoimmune diseases and SSc. Itaconate is a product of the Krebs cycle intermediate cis-aconitate and is an immunomodulator. This work examines the role of the cell-permeable derivative of itaconate, 4-octyl itaconate (4-OI), in SSc. SSc and healthy dermal fibroblasts were exposed to 4-OI. The levels of collagen Nrf2-target genes and pro-inflammatory cytokines interleukin 6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) were determined. Levels of reactive oxygen species (ROS) as well as the gene expression of collagen and Cellular Communication Network Factor 2 (CCN2) were measured after transforming growth factor beta 1 (TGF-β1) stimulation in the presence or absence of 4-OI. Wild-type or Nrf2-knockout (Nrf2-KO) mouse embryonic fibroblasts (MEFs) were also treated with 4-OI to determine the role of Nrf2 in 4-OI-mediated effects. 4-OI reduced the levels of collagen in SSc dermal fibroblasts. Incubation with 4-OI led to activation of Nrf2 and its target genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). 4-OI activated antioxidant response element (ARE)-dependent gene expression, reduced inflammatory cytokine release and reduced TGF-β1-induced collagen and ROS production in dermal fibroblasts. The effects of 4-OI are dependent on Nrf2. The cell-permeable derivative of itaconate 4-OI is anti-fibrotic through upregulation of Nrf2 and could be a potential therapeutic option in an intractable disease.

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HUBUNGAN ANTARA KADAR TGF-Β1 DENGAN KADAR ALBUMIN DALAM URIN PASIEN DM TIPE-2 DENGAN NEFROPATI DIABETIK

JAMBI MEDICAL JOURNAL Jurnal Kedokteran dan Kesehatan ◽

10.22437/jmj.v7i1.7070 ◽

2019 ◽

Vol 7 (1) ◽

pp. 73-81

Author(s):

Elfiani Elfiani ◽

Rita Halim ◽

M Haldian Hakir

Keyword(s):

Diabetic Nephropathy ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Albumin Level ◽

Cross Sectional ◽

Integrin Linked Kinase ◽

Tgf Β1

ABSTRACT Background: Diabetic nephropathy (DN) is a complication of diabetes in the kidney that frequently causes terminal kidney disease. This kidney disease caused by diabetes is a syndrome characterized by albumin in urine (albuminuria). Growth factor-β1 (TGF- β1) is a multifunctional cytokine that controls many biological processes, including immunity, differentiation, tumor suppression, tumor metastasis, aging, migration, wound healing, apoptosis, adipogenesis, and osteogenesis. Previous studies had showed that TGF-β1 plays a role in albuminuria, where TGF-β1 expression in the kidney increases in diabetes patients. Elevation of cytokine level, especially transforming growth factor beta-1 (TGF-β1) that induces the increase of several extra cellular matrices (ECM), i.e. fibronectin, integrin-linked kinase (ILK) and type IV collagen. This TGF-β1 activity causes the accumulation of ECM, which leads to thickened glomerular basement membrane (GBM). Thickening of GBM and changes in kidney structure in the form of hypertrophy and reduced glomerular podocytes caused by apoptosis and attachment in GBM causes protein components to exit through urine (albuminuria). This study aimed to prove the correlation between transforming growth factor-β1 and albumin level in urine of diabetic nephropathy. Metode : This study a observasional with desain Cross-sectional comparative study. Results: Mean TGF-β1 level in type 2 DM patients with diabetic nephropathy in this study was 47.30 ± 14.70 ng/ml, with similar value between men and women with 43.1 ng/ml and 44.7 ng/ml, respectively. Out of 60 type 2 DM participants with ND, the mean albuminuria level according to ACR was 722.53 ± 1854.96 mg/g. The result of male participants was lower compared to female participants, with 667.8 mg/mg and 777.2 mg/g, respectively. Conclusion: There was insignificant correlation between TGF-β1 in diabetic nephropathy (DN) and albumin level in urine measured using albumin and urine creatinine ratio (ACR) (p = 0.066). Keywords: Diabetic Nephropathy, Albuminuria, TGF-β1 ABSTRAK Latar Belakang : Nefropati diabetik (ND) merupakan komplikasi diabetes pada ginjal yang paling sering menyebabkan terjadinya penyakit ginjal terminal. Penyakit ginjal akibat diabetes ini merupakan sindroma dengan karakteristik terdapatnya albumin dalam urine (albuminuria). Faktor pertumbuhan-β1 (TGF-β1) adalah sebuah sitokin multifungsi yang mengendalikan banyak proses biologis termasuk kekebalan, diferensiasi, tumor supresi, tumor metastasis, penuaan, migrasi, penyembuhan luka, apoptosis, adipogenesis, dan osteogenesis. Sejumlah penelitian sebelumnya menunjukkan bahwa TGF-β1 berperan terhadap terjadinya albuminuria, dimana pasien diabetes didapatkan ekspresi TGF-β1 di ginjal meningkat. Peningkatan kadar cytokine terutama Transforming Growth Factor Beta-1 (TGF-β1) yang menginduksi peningkatan beberapa Extra Cellular Matrix (ECM) antara lain fibronectin, integrin-linked kinase (ILK) dan collagen tipe-IV. Aktifitas TGF-β1 ini menyebabkan akumulasi ECM sehingga terjadi penebalan Glomerular Basement Membrane (GBM). Penebalan dari GBM dan terjadinya perubahan struktur ginjal berupa hipertrofi dan berkurangnya sel-sel podocyte glomerulus akibat kerusakan (apoptosis) dan perlengketan di GBM menyebabkan komponen protein keluar melalui urin (albuminuria). Tujuan penelitian ini untuk membuktikan hubungan antara kadar transforming growth factor-β1 dengan kadar albumin dalam urin pada Nefropati Diabetik. Metode : Penelitian ini merupakan penelitian Observasional dengan desain Cross-sectional comparative study. Hasil : Kadar rata-rata TGF-β1 pasien DM tipe-2 dengan Nefropati Diabetik pada penelitian ini adalah 47,30 ± 14,70 ng/ml, tidak jauh berbeda antara laki-laki yaitu 43,1 ng/ml dengan perempuan 44,7 ng/ml. Dari 60 orang responden DM tipe-2 dengan ND pada penelitian ini didapatkan kadar albuminuria rata-rata berdasarkan ACR adalah 722,53 ± 1854,96 mg/g. Responden laki-laki lebih rendah dibanding perempuan yaitu 667,8 mg/g berbanding 777,2 mg/g. Kesimpulan : Tidak terdapat hubungan yang bermakna antara TGF-β1 pada Nefropati Diabetik (ND) dengan kadar albumin dalam urin yang dihitung berdasarkan rasio albumin dan creatinin urin (ACR) (p=0,066). Kata Kunci : Nefropati Diabetik, Albuminuria, TGF-β1

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Cafestol Inhibits High-Glucose-Induced Cardiac Fibrosis in Cardiac Fibroblasts and Type 1-Like Diabetic Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4503747 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Ju-Chi Liu ◽

Po-Yuan Chen ◽

Wen-Rui Hao ◽

Yi-Chung Liu ◽

Ping-Chiang Lyu ◽

...

Keyword(s):

High Glucose ◽

Collagen Synthesis ◽

Cardiac Fibrosis ◽

Cardiac Fibroblasts ◽

Biological Effects ◽

Diabetic Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Tgf Β1

Diabetes is associated with the development of myocardial fibrosis, which is related to various cardiac diseases. Cafestol, one of the active ingredients in coffee, has been reported to exert biological effects. However, whether cafestol can ameliorate diabetes-induced cardiac fibrosis remains unknown. The aim of this study was to evaluate the effects of cafestol on cardiac fibrosis in high-glucose-treated cardiac fibroblasts and streptozocin- (STZ-) induced diabetic rats. Rat cardiac fibroblasts were cultured in high-glucose (25 mM) media in the absence or presence of cafestol, and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production, and related signaling molecules were assessed on the basis of 3H-proline incorporation, enzyme-linked immunosorbent assay, and western blotting. Cardiac fibroblasts exposed to high-glucose conditions exhibited increased collagen synthesis, TGF-β1 production, and Smad2/3 phosphorylation, and these effects were mitigated by cafestol treatment. Furthermore, cafestol increased the translocation of nuclear factor erythroid 2-related factor 2 and increased the expression of heme oxygenase-1. The results of molecular docking analysis suggested a selective interaction of cafestol with Kelch-like ECH-associated protein 1. The rats with untreated STZ-induced diabetes exhibited considerable collagen accumulation, which was ameliorated by cafestol. Moreover, activities of catalase, superoxide dismutase, general matrix metalloproteinase, and reduced glutathione concentration were upregulated, whereas malondialdehyde level was downregulated by treatment with cafestol in rats with cardiac fibrosis. These findings highlight the effects of cafestol, which may be useful in treating diabetes-related cardiac fibrosis.

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Streptozocin Diabetes Elevates all Isoforms of TGF-β in the Rat Kidney

International Journal of Experimental Diabetes Research ◽

10.1155/edr.2001.55 ◽

2001 ◽

Vol 2 (1) ◽

pp. 55-62 ◽

Cited By ~ 10

Author(s):

Pascale H. Lane ◽

Dustin M. Snelling ◽

William J. Langer

Keyword(s):

Diabetic Nephropathy ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Rat Kidney ◽

Fold Increase ◽

Diabetic Rat ◽

The Impact ◽

Tgf Β1

Transforming growth factor beta (TGF-β) is a major promoter of diabetic nephropathy. While TGF-β1 is the most abundaft renal isoform, types 2 and 3 are present as well and have identicalin vitroeffects. Whole kidney extracts were studied 2 weeks after induction of streptozocin diabetes and in control rats. Mean glomerular area was 25% greater in the diabetic animals. TGF-β1 showed a 2-fold increase in message with a 3-fold increase in protein. TGF-β2 mRNA increased approximately 6% while its protein doubled. TGF-β-message increased by 25%, producing a 35% increase in its protein. TGF-β- inducible gene H3 mRNA was increased 35% in the diabetic animals, consistent with increased activity of this growth factor. All isoforms of TGF-β are increased in the diabetic rat kidney. Future studies need to address the specific role that each isoform plays in diabetic nephropathy as well as the impact of therapies on each isoform.

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Non-Invasive Urinary Markers of Renal Dysfunction in Sickle Cell Disease.

Blood ◽

10.1182/blood.v114.22.4621.4621 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4621-4621

Author(s):

Davoud Mohtat ◽

Thomas Moulton ◽

M. Catherine Driscoll ◽

Robert P Woroniecki

Keyword(s):

Sickle Cell Disease ◽

Renal Disease ◽

Urinary Excretion ◽

Sickle Cell ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Conflicts Of Interest ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Disease ◽

Tgf Β1

Abstract Abstract 4621 Renal failure is one of the major complications of sickle cell disease (SCD), affecting 5-18% of the patients. Microalbuminuria (MA), which has a prevalence of 26.5% in all children with SCD, is used as a marker of preclinical glomerular damage and renal disease progression. However, measuring MA alone may miss renal damage involving tubular proteins. We hypothesize that sickle cell nephropathy subjects will have increased urinary excretion of Transforming Growth Factor Beta-1 (TGF β1) and Neutrophil Gelatinase–Associated Lipocalin (NGAL) as compared to age-matched controls (CTR). We also hypothesize that urinary excretion of these proteins will be associated with severity of anemia in SCD. Enzyme-Linked Immunosorbent Assay (ELISA) kits were used to detect urinary excretion of TGF β1/NGAL, and corrected to urine creatinine. Mean age, gender, and race were not statistically different among the groups. Urinary excretion of TGF β1 was significantly higher in SCD subjects (26.4 pg/mg Cr +/-1.5) vs. CTR (14.9 pg/mg Cr +/-2.4), (p<0.00001). There was no difference in urinary NGAL between the SCD subjects vs. CTR. SCD patients with hemoglobin less than 9gm/dl had higher urinary TGF β1 than SCD patients with milder anemia (p=0.002). Urinary TGF β1 was lower in SCD patients on hydroxyurea (23.61+/-2.6), vs. those who were (27.69+/-1.8), p=0.08. Surprisingly, there were no correlation between urinary TGF β1 and urinary microalbumin or estimated glomerular function, indicating that microalbuminuria and serum creatinine are poor measures of renal injury in SCD patients. Our data suggests that urinary TGF β1 may serve as a urinary biomarker to monitor the progression of renal disease in SCD. This assumption needs to be tested prospectively. Disclosures: No relevant conflicts of interest to declare.

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Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-β1/Smad Pathways

Cellular Physiology and Biochemistry ◽

10.1159/000481847 ◽

2017 ◽

Vol 43 (4) ◽

pp. 1359-1368 ◽

Cited By ~ 11

Author(s):

Lifen Du ◽

Yongfang Lei ◽

Jinglou Chen ◽

Hongping Song ◽

Xinying Wu

Keyword(s):

Oxidative Stress ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Smooth Muscle Actin ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Type I ◽

Protective Effects ◽

Mesenchymal Transition ◽

Tgf Β1

Background/Aims: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Method: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. Results: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. Conclusion: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways.

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