The Association Between Oxidative Stress Alleviation via Sulforaphane-Induced Nrf2-HO-1/NQO-1 Signaling Pathway Activation and Chronic Renal Allograft Dysfunction Improvement
Background/Aims: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be...
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| Veröffentlicht in: | Kidney & blood pressure research 2018-01, Vol.43 (1), p.191-205 |
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| creator | Lv, Daoyuan Zhou, Qin Xia, Yue You, Xu Zhao, Zhihong Li, Yongqiang Zou, Hequn |
| description | Background/Aims: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement. Methods: F344 rat kidneys were orthotopically transplanted into Lewis rat recipients to establish CRAD models. Sulforaphane was administered at 1.5 mg/kg intraperitoneally once daily. Renal function and 24-hour urinary protein were monitored for variations for 24 weeks after transplantation. After 24 weeks, renal histopathology was evaluated according to the Banff criteria after hematoxylin and eosin, Masson’s trichrome and periodic acid-Schiff stainings. Additionally, intrarenal oxidative stress was assessed by the indicators malondialdehyde, 8-isoprostane, oxidized-low density lipoprotein and 8-hydroxy-2’-deoxyguanosine, as well as the activity levels of the antioxidant enzymes total superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and γ-glutamylcysteine synthetase. Nrf2, HO-1 and NQO-1 expression levels were determined via immunohistochemical and Western blot analyses. Results: The sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation, as demonstrated by immunohistochemical and Western blot analyses, delayed the progression of serum creatinine and blood urea nitrogen, particularly lowering the 24-hour urinary protein levels of CRAD. The semi-quantified histopathological changes were also alleviated. Evidence of oxidative stress alleviation, as indicated by a concurrent decrease in the indicators and sustained levels of antioxidant enzymes activity, was found in the renal allografts after sulforaphane intervention. Conclusion: Oxidative stress alleviation caused by continuous sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation is associated with functional and morphological improvements of CRAD. |
| doi_str_mv | 10.1159/000487501 |
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Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement. Methods: F344 rat kidneys were orthotopically transplanted into Lewis rat recipients to establish CRAD models. Sulforaphane was administered at 1.5 mg/kg intraperitoneally once daily. Renal function and 24-hour urinary protein were monitored for variations for 24 weeks after transplantation. After 24 weeks, renal histopathology was evaluated according to the Banff criteria after hematoxylin and eosin, Masson’s trichrome and periodic acid-Schiff stainings. Additionally, intrarenal oxidative stress was assessed by the indicators malondialdehyde, 8-isoprostane, oxidized-low density lipoprotein and 8-hydroxy-2’-deoxyguanosine, as well as the activity levels of the antioxidant enzymes total superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and γ-glutamylcysteine synthetase. Nrf2, HO-1 and NQO-1 expression levels were determined via immunohistochemical and Western blot analyses. Results: The sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation, as demonstrated by immunohistochemical and Western blot analyses, delayed the progression of serum creatinine and blood urea nitrogen, particularly lowering the 24-hour urinary protein levels of CRAD. The semi-quantified histopathological changes were also alleviated. Evidence of oxidative stress alleviation, as indicated by a concurrent decrease in the indicators and sustained levels of antioxidant enzymes activity, was found in the renal allografts after sulforaphane intervention. Conclusion: Oxidative stress alleviation caused by continuous sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation is associated with functional and morphological improvements of CRAD.</description><identifier>ISSN: 1420-4096</identifier><identifier>EISSN: 1423-0143</identifier><identifier>DOI: 10.1159/000487501</identifier><identifier>PMID: 29466800</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Allografts ; Animal models ; Animals ; Antioxidants ; Atrophy ; Catalase ; Chronic renal allograft dysfunction ; Creatinine ; Deoxyguanosine ; Enzymes ; Fibrosis ; Free radicals ; Gene expression ; Glutathione ; Glutathione peroxidase ; Glutathione reductase ; Heme Oxygenase (Decyclizing) - metabolism ; Histopathology ; Indicators ; Intervention ; Ischemia ; Isothiocyanates - pharmacology ; Kidney diseases ; Kidney transplantation ; Kidney Transplantation - standards ; Kidneys ; Laboratory animals ; Low density lipoprotein ; Malondialdehyde ; Morphology ; NAD(P)H Dehydrogenase (Quinone) ; NF-E2-Related Factor 2 - metabolism ; Nitric oxide ; Nrf2 ; Original Paper ; Oxidative stress ; Oxidative Stress - drug effects ; Peroxidase ; Proteins ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Renal function ; Rodents ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Sulforaphane ; Superoxide dismutase ; Transplantation ; Transplants & implants ; Urea ; Urine ; γ-Glutamylcysteine</subject><ispartof>Kidney & blood pressure research, 2018-01, Vol.43 (1), p.191-205</ispartof><rights>2018 The Author(s). Published by S. Karger AG, Basel</rights><rights>2018 The Author(s). Published by S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-a926865d9d7ecb2406c77d97f4deab0619b7bc1f546ecbc179bcc6b73d00b1fe3</citedby><cites>FETCH-LOGICAL-c463t-a926865d9d7ecb2406c77d97f4deab0619b7bc1f546ecbc179bcc6b73d00b1fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,2102,27635,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29466800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lv, Daoyuan</creatorcontrib><creatorcontrib>Zhou, Qin</creatorcontrib><creatorcontrib>Xia, Yue</creatorcontrib><creatorcontrib>You, Xu</creatorcontrib><creatorcontrib>Zhao, Zhihong</creatorcontrib><creatorcontrib>Li, Yongqiang</creatorcontrib><creatorcontrib>Zou, Hequn</creatorcontrib><title>The Association Between Oxidative Stress Alleviation via Sulforaphane-Induced Nrf2-HO-1/NQO-1 Signaling Pathway Activation and Chronic Renal Allograft Dysfunction Improvement</title><title>Kidney & blood pressure research</title><addtitle>Kidney Blood Press Res</addtitle><description>Background/Aims: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement. Methods: F344 rat kidneys were orthotopically transplanted into Lewis rat recipients to establish CRAD models. Sulforaphane was administered at 1.5 mg/kg intraperitoneally once daily. Renal function and 24-hour urinary protein were monitored for variations for 24 weeks after transplantation. After 24 weeks, renal histopathology was evaluated according to the Banff criteria after hematoxylin and eosin, Masson’s trichrome and periodic acid-Schiff stainings. Additionally, intrarenal oxidative stress was assessed by the indicators malondialdehyde, 8-isoprostane, oxidized-low density lipoprotein and 8-hydroxy-2’-deoxyguanosine, as well as the activity levels of the antioxidant enzymes total superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and γ-glutamylcysteine synthetase. Nrf2, HO-1 and NQO-1 expression levels were determined via immunohistochemical and Western blot analyses. Results: The sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation, as demonstrated by immunohistochemical and Western blot analyses, delayed the progression of serum creatinine and blood urea nitrogen, particularly lowering the 24-hour urinary protein levels of CRAD. The semi-quantified histopathological changes were also alleviated. Evidence of oxidative stress alleviation, as indicated by a concurrent decrease in the indicators and sustained levels of antioxidant enzymes activity, was found in the renal allografts after sulforaphane intervention. Conclusion: Oxidative stress alleviation caused by continuous sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation is associated with functional and morphological improvements of CRAD.</description><subject>Allografts</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Atrophy</subject><subject>Catalase</subject><subject>Chronic renal allograft dysfunction</subject><subject>Creatinine</subject><subject>Deoxyguanosine</subject><subject>Enzymes</subject><subject>Fibrosis</subject><subject>Free radicals</subject><subject>Gene expression</subject><subject>Glutathione</subject><subject>Glutathione peroxidase</subject><subject>Glutathione reductase</subject><subject>Heme Oxygenase (Decyclizing) - metabolism</subject><subject>Histopathology</subject><subject>Indicators</subject><subject>Intervention</subject><subject>Ischemia</subject><subject>Isothiocyanates - pharmacology</subject><subject>Kidney diseases</subject><subject>Kidney transplantation</subject><subject>Kidney Transplantation - standards</subject><subject>Kidneys</subject><subject>Laboratory animals</subject><subject>Low density lipoprotein</subject><subject>Malondialdehyde</subject><subject>Morphology</subject><subject>NAD(P)H Dehydrogenase (Quinone)</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nitric oxide</subject><subject>Nrf2</subject><subject>Original Paper</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Peroxidase</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Rats, Inbred Lew</subject><subject>Renal function</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Sulforaphane</subject><subject>Superoxide dismutase</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Urea</subject><subject>Urine</subject><subject>γ-Glutamylcysteine</subject><issn>1420-4096</issn><issn>1423-0143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DOA</sourceid><recordid>eNptkkuP0zAQgCMEYh9w4I6Qpb0sh7C249j1sVseW7HawnY5R449blOSuNhJl_4pfiNuU4qEuHis8advxqNJklcEvyMkl1cYYzYSOSZPklPCaJZiwrKn-ztOGZb8JDkLYRWxHGP6PDmhknE-wvg0-fWwBDQOwelKdZVr0TV0jwAtmv2sTMxsAM07DyGgcV3D5gDFiOZ9bZ1X66VqIZ22ptdg0J23NL2ZpeTq7ms80bxatKqu2gX6orrlo9qisY7SwaJagyZL79pKo3uI3K6GW3hlO_R-G2zf6j03bdbebaCBtnuRPLOqDvDyEM-Tbx8_PExu0tvZp-lkfJtqxrMuVZLyEc-NNAJ0SRnmWggjhWUGVIk5kaUoNbE54_FdEyFLrXkpMoNxSSxk58l08BqnVsXaV43y28KpqtgnnF8UyneVrqEoBSNg8zxnJmeaS6kEpYoCttISprPouhxc8Rc_eghd0VRBQ13Hwbk-FBRjwSgXdBTRi3_Qlet9nEykCBEk55nYUW8HSnsXggd7bJDgYrcQxXEhIvvmYOzLBsyR_LMBf0t-V34B_gh8vr4fFMXa2Ei9_i91qPIbC-jGRw</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Lv, Daoyuan</creator><creator>Zhou, Qin</creator><creator>Xia, Yue</creator><creator>You, Xu</creator><creator>Zhao, Zhihong</creator><creator>Li, Yongqiang</creator><creator>Zou, Hequn</creator><general>S. Karger AG</general><general>Karger Publishers</general><scope>M--</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20180101</creationdate><title>The Association Between Oxidative Stress Alleviation via Sulforaphane-Induced Nrf2-HO-1/NQO-1 Signaling Pathway Activation and Chronic Renal Allograft Dysfunction Improvement</title><author>Lv, Daoyuan ; Zhou, Qin ; Xia, Yue ; You, Xu ; Zhao, Zhihong ; Li, Yongqiang ; Zou, Hequn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-a926865d9d7ecb2406c77d97f4deab0619b7bc1f546ecbc179bcc6b73d00b1fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Allografts</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Atrophy</topic><topic>Catalase</topic><topic>Chronic renal allograft dysfunction</topic><topic>Creatinine</topic><topic>Deoxyguanosine</topic><topic>Enzymes</topic><topic>Fibrosis</topic><topic>Free radicals</topic><topic>Gene expression</topic><topic>Glutathione</topic><topic>Glutathione peroxidase</topic><topic>Glutathione reductase</topic><topic>Heme Oxygenase (Decyclizing) - metabolism</topic><topic>Histopathology</topic><topic>Indicators</topic><topic>Intervention</topic><topic>Ischemia</topic><topic>Isothiocyanates - pharmacology</topic><topic>Kidney diseases</topic><topic>Kidney transplantation</topic><topic>Kidney Transplantation - standards</topic><topic>Kidneys</topic><topic>Laboratory animals</topic><topic>Low density lipoprotein</topic><topic>Malondialdehyde</topic><topic>Morphology</topic><topic>NAD(P)H Dehydrogenase (Quinone)</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nitric oxide</topic><topic>Nrf2</topic><topic>Original Paper</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Peroxidase</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Rats, Inbred Lew</topic><topic>Renal function</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>Sulforaphane</topic><topic>Superoxide dismutase</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><topic>Urea</topic><topic>Urine</topic><topic>γ-Glutamylcysteine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lv, Daoyuan</creatorcontrib><creatorcontrib>Zhou, Qin</creatorcontrib><creatorcontrib>Xia, Yue</creatorcontrib><creatorcontrib>You, Xu</creatorcontrib><creatorcontrib>Zhao, Zhihong</creatorcontrib><creatorcontrib>Li, Yongqiang</creatorcontrib><creatorcontrib>Zou, Hequn</creatorcontrib><collection>Karger Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Kidney & blood pressure research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lv, Daoyuan</au><au>Zhou, Qin</au><au>Xia, Yue</au><au>You, Xu</au><au>Zhao, Zhihong</au><au>Li, Yongqiang</au><au>Zou, Hequn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Association Between Oxidative Stress Alleviation via Sulforaphane-Induced Nrf2-HO-1/NQO-1 Signaling Pathway Activation and Chronic Renal Allograft Dysfunction Improvement</atitle><jtitle>Kidney & blood pressure research</jtitle><addtitle>Kidney Blood Press Res</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>43</volume><issue>1</issue><spage>191</spage><epage>205</epage><pages>191-205</pages><issn>1420-4096</issn><eissn>1423-0143</eissn><abstract>Background/Aims: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement. Methods: F344 rat kidneys were orthotopically transplanted into Lewis rat recipients to establish CRAD models. Sulforaphane was administered at 1.5 mg/kg intraperitoneally once daily. Renal function and 24-hour urinary protein were monitored for variations for 24 weeks after transplantation. After 24 weeks, renal histopathology was evaluated according to the Banff criteria after hematoxylin and eosin, Masson’s trichrome and periodic acid-Schiff stainings. Additionally, intrarenal oxidative stress was assessed by the indicators malondialdehyde, 8-isoprostane, oxidized-low density lipoprotein and 8-hydroxy-2’-deoxyguanosine, as well as the activity levels of the antioxidant enzymes total superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and γ-glutamylcysteine synthetase. Nrf2, HO-1 and NQO-1 expression levels were determined via immunohistochemical and Western blot analyses. Results: The sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation, as demonstrated by immunohistochemical and Western blot analyses, delayed the progression of serum creatinine and blood urea nitrogen, particularly lowering the 24-hour urinary protein levels of CRAD. The semi-quantified histopathological changes were also alleviated. Evidence of oxidative stress alleviation, as indicated by a concurrent decrease in the indicators and sustained levels of antioxidant enzymes activity, was found in the renal allografts after sulforaphane intervention. Conclusion: Oxidative stress alleviation caused by continuous sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation is associated with functional and morphological improvements of CRAD.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>29466800</pmid><doi>10.1159/000487501</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Allografts Animal models Animals Antioxidants Atrophy Catalase Chronic renal allograft dysfunction Creatinine Deoxyguanosine Enzymes Fibrosis Free radicals Gene expression Glutathione Glutathione peroxidase Glutathione reductase Heme Oxygenase (Decyclizing) - metabolism Histopathology Indicators Intervention Ischemia Isothiocyanates - pharmacology Kidney diseases Kidney transplantation Kidney Transplantation - standards Kidneys Laboratory animals Low density lipoprotein Malondialdehyde Morphology NAD(P)H Dehydrogenase (Quinone) NF-E2-Related Factor 2 - metabolism Nitric oxide Nrf2 Original Paper Oxidative stress Oxidative Stress - drug effects Peroxidase Proteins Rats Rats, Inbred F344 Rats, Inbred Lew Renal function Rodents Signal transduction Signal Transduction - drug effects Signaling Sulforaphane Superoxide dismutase Transplantation Transplants & implants Urea Urine γ-Glutamylcysteine |
| title | The Association Between Oxidative Stress Alleviation via Sulforaphane-Induced Nrf2-HO-1/NQO-1 Signaling Pathway Activation and Chronic Renal Allograft Dysfunction Improvement |
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