N-Acetylcysteine Attenuates the Development of Renal Fibrosis in Transgenic Mice with Dilated Cardiomyopathy

Beverly Giam, Sanjaya Kuruppu, Po Yin Chu, A. Ian Smith, Francine Z. Marques, April Fiedler, Duncan Horlock, Helen Kiriazis, Xiao-Jun Du, David M. Kaye, Niwanthi W. Rajapakse

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Mechanisms underlying the renal pathology in cardiorenal syndrome (CRS) type 2 remain elusive. We hypothesised that renal glutathione deficiency is central to the development of CRS type 2. Glutathione precursor, N-acetylcysteine (NAC;40 mg/kg/day; 8 weeks) or saline were administered to transgenic mice with dilated cardiomyopathy (DCM) and wild-type (WT) controls. Cardiac structure, function and glutathione levels were assessed at the end of this protocol. Renal fibrosis, glutathione content, expression of inflammatory and fibrotic markers, and function were also evaluated. In both genotypes, NAC had minimal effect on cardiac glutathione, structure and function (P ≥ 0.20). In NAC treated DCM mice, loss of glomerular filtration rate (GFR), tubulointerstitial and glomerular fibrosis and renal oxidised glutathione levels were attenuated by 38%, 99%, 70% and 52% respectively, compared to saline treated DCM mice (P ≤ 0.01). Renal expression of PAI-1 was greater in saline treated DCM mice than in WT mice (P < 0.05). Renal PAI-1 expression was less in NAC treated DCM mice than in vehicle treated DCM mice (P = 0.03). Renal IL-10 expression was greater in the former cohort compared to the latter (P < 0.01). These data indicate that normalisation of renal oxidized glutathione levels attenuates PAI-1 expression and renal inflammation preventing loss of GFR in experimental DCM.

Original languageEnglish
Article number17718
Number of pages12
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 18 Dec 2017

Keywords

  • kidney
  • preclinical research

Cite this

Giam, Beverly ; Kuruppu, Sanjaya ; Chu, Po Yin ; Smith, A. Ian ; Marques, Francine Z. ; Fiedler, April ; Horlock, Duncan ; Kiriazis, Helen ; Du, Xiao-Jun ; Kaye, David M. ; Rajapakse, Niwanthi W. / N-Acetylcysteine Attenuates the Development of Renal Fibrosis in Transgenic Mice with Dilated Cardiomyopathy. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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abstract = "Mechanisms underlying the renal pathology in cardiorenal syndrome (CRS) type 2 remain elusive. We hypothesised that renal glutathione deficiency is central to the development of CRS type 2. Glutathione precursor, N-acetylcysteine (NAC;40 mg/kg/day; 8 weeks) or saline were administered to transgenic mice with dilated cardiomyopathy (DCM) and wild-type (WT) controls. Cardiac structure, function and glutathione levels were assessed at the end of this protocol. Renal fibrosis, glutathione content, expression of inflammatory and fibrotic markers, and function were also evaluated. In both genotypes, NAC had minimal effect on cardiac glutathione, structure and function (P ≥ 0.20). In NAC treated DCM mice, loss of glomerular filtration rate (GFR), tubulointerstitial and glomerular fibrosis and renal oxidised glutathione levels were attenuated by 38{\%}, 99{\%}, 70{\%} and 52{\%} respectively, compared to saline treated DCM mice (P ≤ 0.01). Renal expression of PAI-1 was greater in saline treated DCM mice than in WT mice (P < 0.05). Renal PAI-1 expression was less in NAC treated DCM mice than in vehicle treated DCM mice (P = 0.03). Renal IL-10 expression was greater in the former cohort compared to the latter (P < 0.01). These data indicate that normalisation of renal oxidized glutathione levels attenuates PAI-1 expression and renal inflammation preventing loss of GFR in experimental DCM.",
keywords = "kidney, preclinical research",
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year = "2017",
month = "12",
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doi = "10.1038/s41598-017-17927-5",
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N-Acetylcysteine Attenuates the Development of Renal Fibrosis in Transgenic Mice with Dilated Cardiomyopathy. / Giam, Beverly; Kuruppu, Sanjaya; Chu, Po Yin; Smith, A. Ian; Marques, Francine Z.; Fiedler, April; Horlock, Duncan; Kiriazis, Helen; Du, Xiao-Jun; Kaye, David M.; Rajapakse, Niwanthi W.

In: Scientific Reports, Vol. 7, No. 1, 17718, 18.12.2017.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Giam, Beverly

AU - Kuruppu, Sanjaya

AU - Chu, Po Yin

AU - Smith, A. Ian

AU - Marques, Francine Z.

AU - Fiedler, April

AU - Horlock, Duncan

AU - Kiriazis, Helen

AU - Du, Xiao-Jun

AU - Kaye, David M.

AU - Rajapakse, Niwanthi W.

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