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GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Ameliorates Renal Damage Associated with Chronic Obstructive Uropathy.
Lin, Shouzhe; Visram, Fazil; Liu, Weihua; Haig, Aaron; Jiang, Jifu; Mok, Amy; Lian, Dameng; Wood, Mark E; Torregrossa, Robert; Whiteman, Matthew; Lobb, Ian; Sener, Alp.
Afiliação
  • Lin S; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada.
  • Visram F; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada.
  • Liu W; Department of Pathology, University of Western Ontario, London, Ontario, Canada.
  • Haig A; Department of Pathology, University of Western Ontario, London, Ontario, Canada.
  • Jiang J; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada.
  • Mok A; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
  • Lian D; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada.
  • Wood ME; School of Biosciences, University of Exeter, Exeter, United Kingdom.
  • Torregrossa R; Medical School, University of Exeter, Exeter, United Kingdom.
  • Whiteman M; Medical School, University of Exeter, Exeter, United Kingdom.
  • Lobb I; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada.
  • Sener A; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada; Department of Surgery, University of Western Ontario, London, Ontario, Canada; Multi-Organ Transplant Program, London Health Sciences Center, London, Ontario, Canada; Matthew Mailing Center for Transla
J Urol ; 196(6): 1778-1787, 2016 12.
Article em En | MEDLINE | ID: mdl-27177428
ABSTRACT

PURPOSE:

Chronic obstructive uropathy can cause irreversible kidney injury, atrophy and inflammation, which can ultimately lead to fibrosis. Epithelial-mesenchymal transition is a key trigger of fibrosis that is caused by up-regulation of TGF-ß1 (transforming growth factor-ß1) and ANGII (angiotensin II). H2S is an endogenously produced gasotransmitter with cytoprotective properties. We sought to elucidate the effects of the slow-releasing H2S donor GYY4137 on chronic ureteral obstruction and evaluate the potential mechanisms. MATERIALS AND

METHODS:

Following unilateral ureteral obstruction male Lewis rats were given daily intraperitoneal administration of phosphate buffered saline vehicle (obstruction group) or phosphate buffered saline plus 200 µmol/kg GYY4137 (obstruction plus GYY4137 group) for 30 days. Urine and serum samples were collected to determine physiological parameters of renal function and injury. Kidneys were removed on postoperative day 30 to evaluate histopathology and protein expression. Epithelial-mesenchymal transition in LLC-PK1 pig kidney epithelial cells was induced with TGF-ß1 and treated with GYY4137 to evaluate potential mechanisms via in vitro scratch wound assays.

RESULTS:

H2S treatment decreased serum creatinine and the urine protein-to-creatinine excretion ratio after unilateral ureteral obstruction. In addition, H2S mitigated cortical loss, inflammatory damage and tubulointerstitial fibrosis. Tissues showed decreased expression of epithelial-mesenchymal transition markers upon H2S treatment. Epithelial-mesenchymal transition progression in LLC-PK1 was alleviated upon in vitro administration of GYY4137.

CONCLUSIONS:

To our knowledge our findings demonstrate for the first time the protective effects of H2S in chronic obstructive uropathy. This may represent a potential therapeutic solution to ameliorate renal damage and improve the clinical outcomes of urinary obstruction.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos Organotiofosforados / Obstrução Ureteral / Morfolinas / Sulfeto de Hidrogênio / Nefropatias Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: J Urol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos Organotiofosforados / Obstrução Ureteral / Morfolinas / Sulfeto de Hidrogênio / Nefropatias Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: J Urol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Canadá