Down-Regulation of TGF-β and VCAM-1 Is Associated With Successful Treatment of Chronic Rejection in Rats

Crews, Gladys; Erickson, Laurie; Fan, Ping; Fisniku, Ogert; Jang, Mei-Shiang; Wynn, Carmen; Benediktsson, Hallgrímur; Kobayashi, Masakazu; Jiang, Hongsi

doi:10.1016/j.transproceed.2005.02.096

Cited by 19 publications

(15 citation statements)

References 8 publications

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“…TGF-␤ itself is a key fibrinogenic cytokine involved in fibrosis in a number of chronic diseases including CAN (29 -31). A correlation between gene expression levels of TGF-␤ and histological changes of chronic rejection and the successful treatment of CAN has been demonstrated in the F344 to LEW model of chronic allograft nephropathy (10). In our experiments, TGF-␤ and PDGF-B expression was lower in allografts that had been treated continuously or late.…”

Section: Discussionsupporting

confidence: 68%

“…In the study of Crews et al (10), a dose of 10 mg/kg/day given for the first 10 days after kidney transplantation also reduced signs of CAN when evaluated 90 days after transplantation.…”

Section: Discussionmentioning

confidence: 92%

“…FK778 has been successfully used in models of acute and chronic rejection, including rat models of CAN (9,10). In contrast to these studies, we focused on the long-term outcome with an observation period of 24 weeks after transplantation.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The Effect of FK778 on the Progression of Chronic Allograft Nephropathy in a Rat Model

Lutz

Huang²,

Deng³

et al. 2007

Transplantation

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Section: Discussionsupporting

confidence: 68%

“…In the study of Crews et al (10), a dose of 10 mg/kg/day given for the first 10 days after kidney transplantation also reduced signs of CAN when evaluated 90 days after transplantation.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

The Effect of FK778 on the Progression of Chronic Allograft Nephropathy in a Rat Model

Lutz

Huang²,

Deng³

et al. 2007

Transplantation

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“…The dosage and method of benazepril [5] and LEF [6] administration were chosen based on previous reports.…”

Section: Methodsmentioning

confidence: 99%

Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

Jin

Piao

Jin

et al. 2014

Nephron Exp Nephrol

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Background: Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. Methods: Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β₁ (TGF-β₁) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. Results: Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β₁ and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. Conclusions: LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.

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“…In the past few years, new watersoluble triptolide derivatives have been designed and synthesized, including PG490-88 or F60008. PG490-88 or F60008, a prodrug of triptolide, is converted to triptolide in vivo by plasma esterases following intravenous administration [59][60][61][62][63][64][65][66][67] . Table 1 summarizes the preclinical pharmacological study of triptolide and PG490-88/F60008 against autoimmune diseases and transplantation rejection.…”

Section: Twhf a Representative Chinese Medicinal Herb Showing Immunomentioning

confidence: 99%

Immunosuppressant discovery from Tripterygium wilfordii Hook f: the novel triptolide analog (5R)-5-hydroxytriptolide (LLDT-8)

Tang

Zuo

2012

Acta Pharmacol Sin

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The Chinese traditional herb Tripterygium wilfordii Hook f (TwHF) has been widely used in the treatment of autoimmune and inflammatory diseases. Over the past few decades, great efforts have been made to explore modern preparations of TwHF with higher efficacy, solubility, and lower toxicity. In this study, we reviewed several examples both of naturally occurring compounds and their derivatives in TwHF, and summarized the preclinical evaluations with regard to autoimmune and inflammatory diseases. All of the candidate compounds described herein have been or are currently in clinical trials. Although some studies encountered problems, the data still provided valuable references for future studies. (5R)-5-hydroxytriptolide (LLDT-8, Leitengshu) is a novel triptolide derivative with potent immunosuppressive and anti-inflammatory activities developed at Shanghai Institute of Materia Medica. Indeed, a Phase I clinical trial for this compound has been completed in rheumatoid arthritis patients. The results will provide the basis for the further exploration of this ancient herb and encourage the research and development of valuable traditional Chinese medicine. IntroductionFor thousands of years, natural products have played an important role throughout the world in treating and preventing human diseases [1][2][3][4][5] . The discovery and development of immunosuppressants from natural sources have an impressive record: mycophenolic acid (MPA) and cyclosporin A (CsA), the fungal metabolites isolated in 1932 [6] and 1970 [7] , respectively; rapamycin, found in 1975 [8] ; FK506, extracted from a culture filtrate of Streptomyces tsukubaensis in 1987 [9,10] ; and fingolimod (FTY720), described in 1995 [11] . Although the current industry model for drug discovery does not favor natural products, the resources are so vast as to seem unlimited, and these emerging tools will provide important discoveries, leading to new medicines [12] . Furthermore, the drugs already in use as immunosuppressants (eg, cyclophosphamide, methotrexate, azathioprine, cyclosporin) are associated with some significant problems, including toxicity, a lack of reversibility, and increased susceptibility to viral and other infections [13] . Indeed, exploring new and innovative immunosuppres-* To whom correspondence should be addressed.E-mail jpzuo@mail.shcnc.ac.cn Received 2012-06-11 Accepted 2012-07-04 sants from natural sources has now become a focus of intense research.Tripterygium wilfordii Hook f (TwHF) and its extracts have been widely used in the treatment of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and dermatomyositis (DM) [14][15][16][17][18] , and have beneficial effects on tissue and organ transplantation [19,20] . In 1993, the ethyl acetate (EA) extract of TwHF was entered into a Phase I study for the treatment of RA patients [21][22][23][24][25] , and many clinical trials have tested triptolide for the treatment of RA and psoriasis [26,27] . In addition, PG490-88/F60008 (F...

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Down-Regulation of TGF-β and VCAM-1 Is Associated With Successful Treatment of Chronic Rejection in Rats

Cited by 19 publications

References 8 publications

The Effect of FK778 on the Progression of Chronic Allograft Nephropathy in a Rat Model

The Effect of FK778 on the Progression of Chronic Allograft Nephropathy in a Rat Model

Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

Immunosuppressant discovery from Tripterygium wilfordii Hook f: the novel triptolide analog (5R)-5-hydroxytriptolide (LLDT-8)

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