Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats

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Author(s)

Abstract

<p>Mineralocorticoid receptor (MR)/NADPH oxidase (NOX) signaling is involved in the development of obesity, insulin resistance, and renal diseases; however, the role of this signaling on steatotic preneoplastic liver lesions is not fully elucidated. We determined the effects of the MR antagonist potassium canrenoate (PC) on MR/NOX signaling in hepatic steatosis and preneoplastic glutathione <i>S</i>-transferase placental form (GST-P)-positive liver foci. Rats were subjected to a two-stage hepatocarcinogenesis model and fed with basal diet or high fat diet (HFD) that was co-administered with PC alone or in combination with the antioxidant alpha-glycosyl isoquercitrin (AGIQ). PC reduced obesity and renal changes (basophilic tubules that expressed MR and p22phox) but did not affect blood glucose tolerance and non-alcoholic fatty liver disease activity score (NAS) in HFD-fed rats. However, the drug increased the area of GST-P-positive liver foci that expressed MR and p22phox as well as increased expression of NOX genes (<i>p22phox</i>, <i>Poldip2</i>, and <i>NOX4</i>). PC in combination with AGIQ had the potential of inhibiting the effects of PC on the area of GST-P-positive liver foci and the effects were associated with increasing expression of an anti-oxidative enzyme (<i>Catalase</i>). The results suggested that MR/NOX signaling might be involved in development of preneoplastic liver foci and renal basophilic changes in HFD-fed rats; however, the impacts of PC were different in each organ.</p>

Journal

  • The Journal of Toxicological Sciences

    The Journal of Toxicological Sciences 43(10), 611-621, 2018

    The Japanese Society of Toxicology

Codes

  • NII Article ID (NAID)
    130007496040
  • NII NACSIS-CAT ID (NCID)
    AN00002808
  • Text Lang
    ENG
  • ISSN
    0388-1350
  • NDL Article ID
    029622134
  • NDL Call No.
    Z19-1022
  • Data Source
    NDL  J-STAGE 
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