Spironolactone in Combination with α-glycosyl Isoquercitrin Prevents Steatosis-related Early Hepatocarcinogenesis in Rats through the Observed NADPH Oxidase Modulation
Administration of the diuretic, spironolactone (SR), can inhibit chronic liver diseases. We determined the effects of SR alone or in combination with the antioxidant α-glycosyl isoquercitrin (AGIQ) on hyperlipidemia- and steatosis-related precancerous lesions in high-fat diet (HFD)-fed rats subjecte...
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| Veröffentlicht in: | Toxicologic pathology 2018-07, Vol.46 (5), p.530-539 |
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| creator | Murayama, Hirotada Eguchi, Ayumi Nakamura, Misato Kawashima, Masahi Nagahara, Rei Mizukami, Sayaka Kimura, Masayuki Makino, Emi Takahashi, Naofumi Ohtsuka, Ryoichi Koyanagi, Mihoko Hayashi, Shim-mo Maronpot, Robert R. Shibutani, Makoto Yoshida, Toshinori |
| description | Administration of the diuretic, spironolactone (SR), can inhibit chronic liver diseases. We determined the effects of SR alone or in combination with the antioxidant α-glycosyl isoquercitrin (AGIQ) on hyperlipidemia- and steatosis-related precancerous lesions in high-fat diet (HFD)-fed rats subjected to a two-stage hepatocarcinogenesis model. Rats were fed with control basal diet or HFD, which was administered with SR alone or in combination with an antioxidant AGIQ in drinking water. An HFD increased body weight, intra-abdominal fat (adipose) tissue weight, and plasma lipids, which were reduced by coadministration of SR and AGIQ. SR and AGIQ coadministration also reduced hepatic steatosis and preneoplastic glutathione S-transferase placental form-positive foci, in association with decrease in NADPH oxidase (NOX) subunit p22phox-positive cells and an increase in active-caspase-3-positive cells in the foci. Hepatic gene expression analysis revealed that the coadministration of SR and AGIQ altered mRNA levels of lipogenic enzymes (Scd1 and Fasn), antioxidant-related enzymes (Catalase), NOX component (P67phox), and anti-inflammatory transcriptional factor (Pparg). Our results indicated that SR in combination with AGIQ had the potential of suppressing hyperlipidemia- and steatosis-related early hepatocarcinogenesis through the reduced expression of NOX subunits. |
| doi_str_mv | 10.1177/0192623318778508 |
| format | Article |
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We determined the effects of SR alone or in combination with the antioxidant α-glycosyl isoquercitrin (AGIQ) on hyperlipidemia- and steatosis-related precancerous lesions in high-fat diet (HFD)-fed rats subjected to a two-stage hepatocarcinogenesis model. Rats were fed with control basal diet or HFD, which was administered with SR alone or in combination with an antioxidant AGIQ in drinking water. An HFD increased body weight, intra-abdominal fat (adipose) tissue weight, and plasma lipids, which were reduced by coadministration of SR and AGIQ. SR and AGIQ coadministration also reduced hepatic steatosis and preneoplastic glutathione S-transferase placental form-positive foci, in association with decrease in NADPH oxidase (NOX) subunit p22phox-positive cells and an increase in active-caspase-3-positive cells in the foci. Hepatic gene expression analysis revealed that the coadministration of SR and AGIQ altered mRNA levels of lipogenic enzymes (Scd1 and Fasn), antioxidant-related enzymes (Catalase), NOX component (P67phox), and anti-inflammatory transcriptional factor (Pparg). Our results indicated that SR in combination with AGIQ had the potential of suppressing hyperlipidemia- and steatosis-related early hepatocarcinogenesis through the reduced expression of NOX subunits.</description><identifier>ISSN: 0192-6233</identifier><identifier>EISSN: 1533-1601</identifier><identifier>DOI: 10.1177/0192623318778508</identifier><identifier>PMID: 29843569</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Body Weight - drug effects ; Diet, High-Fat ; Drug Therapy, Combination ; Fatty Liver - complications ; Fatty Liver - drug therapy ; Fatty Liver - pathology ; Liver Neoplasms, Experimental - etiology ; Liver Neoplasms, Experimental - pathology ; Liver Neoplasms, Experimental - prevention & control ; Male ; NADPH Oxidases - metabolism ; Organ Size - drug effects ; Oxidative Stress - drug effects ; Precancerous Conditions - pathology ; Precancerous Conditions - prevention & control ; Quercetin - administration & dosage ; Quercetin - analogs & derivatives ; Quercetin - therapeutic use ; Rats, Inbred F344 ; Spironolactone - administration & dosage ; Spironolactone - therapeutic use</subject><ispartof>Toxicologic pathology, 2018-07, Vol.46 (5), p.530-539</ispartof><rights>The Author(s) 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c379t-ad0178f0f3d51a73117dc2a9f3b41d33e836b035152a25bb1dbdc515cc44e01c3</citedby><cites>FETCH-LOGICAL-c379t-ad0178f0f3d51a73117dc2a9f3b41d33e836b035152a25bb1dbdc515cc44e01c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0192623318778508$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0192623318778508$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>315,781,785,21824,27929,27930,43626,43627</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29843569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murayama, Hirotada</creatorcontrib><creatorcontrib>Eguchi, Ayumi</creatorcontrib><creatorcontrib>Nakamura, Misato</creatorcontrib><creatorcontrib>Kawashima, Masahi</creatorcontrib><creatorcontrib>Nagahara, Rei</creatorcontrib><creatorcontrib>Mizukami, Sayaka</creatorcontrib><creatorcontrib>Kimura, Masayuki</creatorcontrib><creatorcontrib>Makino, Emi</creatorcontrib><creatorcontrib>Takahashi, Naofumi</creatorcontrib><creatorcontrib>Ohtsuka, Ryoichi</creatorcontrib><creatorcontrib>Koyanagi, Mihoko</creatorcontrib><creatorcontrib>Hayashi, Shim-mo</creatorcontrib><creatorcontrib>Maronpot, Robert R.</creatorcontrib><creatorcontrib>Shibutani, Makoto</creatorcontrib><creatorcontrib>Yoshida, Toshinori</creatorcontrib><title>Spironolactone in Combination with α-glycosyl Isoquercitrin Prevents Steatosis-related Early Hepatocarcinogenesis in Rats through the Observed NADPH Oxidase Modulation</title><title>Toxicologic pathology</title><addtitle>Toxicol Pathol</addtitle><description>Administration of the diuretic, spironolactone (SR), can inhibit chronic liver diseases. 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Hepatic gene expression analysis revealed that the coadministration of SR and AGIQ altered mRNA levels of lipogenic enzymes (Scd1 and Fasn), antioxidant-related enzymes (Catalase), NOX component (P67phox), and anti-inflammatory transcriptional factor (Pparg). Our results indicated that SR in combination with AGIQ had the potential of suppressing hyperlipidemia- and steatosis-related early hepatocarcinogenesis through the reduced expression of NOX subunits.</description><subject>Animals</subject><subject>Body Weight - drug effects</subject><subject>Diet, High-Fat</subject><subject>Drug Therapy, Combination</subject><subject>Fatty Liver - complications</subject><subject>Fatty Liver - drug therapy</subject><subject>Fatty Liver - pathology</subject><subject>Liver Neoplasms, Experimental - etiology</subject><subject>Liver Neoplasms, Experimental - pathology</subject><subject>Liver Neoplasms, Experimental - prevention & control</subject><subject>Male</subject><subject>NADPH Oxidases - metabolism</subject><subject>Organ Size - drug effects</subject><subject>Oxidative Stress - drug effects</subject><subject>Precancerous Conditions - pathology</subject><subject>Precancerous Conditions - prevention & control</subject><subject>Quercetin - administration & dosage</subject><subject>Quercetin - analogs & derivatives</subject><subject>Quercetin - therapeutic use</subject><subject>Rats, Inbred F344</subject><subject>Spironolactone - administration & dosage</subject><subject>Spironolactone - therapeutic use</subject><issn>0192-6233</issn><issn>1533-1601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhi0Eokvhzgn5yCXgiZN1cqyWwlZquxWFc-TYk11XXnuxncK-EVdepM9Uhy0cKvU0suf7__H4J-QtsA8AQnxk0JbzknNohGhq1jwjM6g5L2DO4DmZTe1i6h-RVzHeMAYNVOwlOSrbpuL1vJ2R39c7E7zzVqrkHVLj6MJve-NkMt7RnyZt6N2fYm33yse9pWfR_xgxKJNCRq8C3qJLkV4nlMlHE4uAVibU9FQGu6dL3OV7JbPA-TU6zMg046vMorQJflxvckW66iOG26y7PPl0taSrX0bLiPTC69H-fcpr8mKQNuKbh3pMvn8-_bZYFuerL2eLk_NCcdGmQmoGohnYwHUNUvD8TVqVsh14X4HmHBs-7xmvoS5lWfc96F6rfFKqqpCB4sfk_cF3F6ZNY-q2Jiq0Vjr0Y-xKVomyaivBMsoOqAo-xoBDtwtmK8O-A9ZN-XSP88mSdw_uY79F_V_wL5AMFAcgyjV2N34MLm_7tOE9K4GciA</recordid><startdate>201807</startdate><enddate>201807</enddate><creator>Murayama, Hirotada</creator><creator>Eguchi, Ayumi</creator><creator>Nakamura, Misato</creator><creator>Kawashima, Masahi</creator><creator>Nagahara, Rei</creator><creator>Mizukami, Sayaka</creator><creator>Kimura, Masayuki</creator><creator>Makino, Emi</creator><creator>Takahashi, Naofumi</creator><creator>Ohtsuka, Ryoichi</creator><creator>Koyanagi, Mihoko</creator><creator>Hayashi, Shim-mo</creator><creator>Maronpot, Robert R.</creator><creator>Shibutani, Makoto</creator><creator>Yoshida, Toshinori</creator><general>SAGE Publications</general><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>7X8</scope></search><sort><creationdate>201807</creationdate><title>Spironolactone in Combination with α-glycosyl Isoquercitrin Prevents Steatosis-related Early Hepatocarcinogenesis in Rats through the Observed NADPH Oxidase Modulation</title><author>Murayama, Hirotada ; Eguchi, Ayumi ; Nakamura, Misato ; Kawashima, Masahi ; Nagahara, Rei ; Mizukami, Sayaka ; Kimura, Masayuki ; Makino, Emi ; Takahashi, Naofumi ; Ohtsuka, Ryoichi ; Koyanagi, Mihoko ; Hayashi, Shim-mo ; Maronpot, Robert R. ; Shibutani, Makoto ; Yoshida, Toshinori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c379t-ad0178f0f3d51a73117dc2a9f3b41d33e836b035152a25bb1dbdc515cc44e01c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Body Weight - drug effects</topic><topic>Diet, High-Fat</topic><topic>Drug Therapy, Combination</topic><topic>Fatty Liver - complications</topic><topic>Fatty Liver - drug therapy</topic><topic>Fatty Liver - pathology</topic><topic>Liver Neoplasms, Experimental - etiology</topic><topic>Liver Neoplasms, Experimental - pathology</topic><topic>Liver Neoplasms, Experimental - prevention & control</topic><topic>Male</topic><topic>NADPH Oxidases - metabolism</topic><topic>Organ Size - drug effects</topic><topic>Oxidative Stress - drug effects</topic><topic>Precancerous Conditions - pathology</topic><topic>Precancerous Conditions - prevention & control</topic><topic>Quercetin - administration & dosage</topic><topic>Quercetin - analogs & derivatives</topic><topic>Quercetin - therapeutic use</topic><topic>Rats, Inbred F344</topic><topic>Spironolactone - administration & dosage</topic><topic>Spironolactone - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murayama, Hirotada</creatorcontrib><creatorcontrib>Eguchi, Ayumi</creatorcontrib><creatorcontrib>Nakamura, Misato</creatorcontrib><creatorcontrib>Kawashima, Masahi</creatorcontrib><creatorcontrib>Nagahara, Rei</creatorcontrib><creatorcontrib>Mizukami, Sayaka</creatorcontrib><creatorcontrib>Kimura, Masayuki</creatorcontrib><creatorcontrib>Makino, Emi</creatorcontrib><creatorcontrib>Takahashi, Naofumi</creatorcontrib><creatorcontrib>Ohtsuka, Ryoichi</creatorcontrib><creatorcontrib>Koyanagi, Mihoko</creatorcontrib><creatorcontrib>Hayashi, Shim-mo</creatorcontrib><creatorcontrib>Maronpot, Robert R.</creatorcontrib><creatorcontrib>Shibutani, Makoto</creatorcontrib><creatorcontrib>Yoshida, Toshinori</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Toxicologic pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murayama, Hirotada</au><au>Eguchi, Ayumi</au><au>Nakamura, Misato</au><au>Kawashima, Masahi</au><au>Nagahara, Rei</au><au>Mizukami, Sayaka</au><au>Kimura, Masayuki</au><au>Makino, Emi</au><au>Takahashi, Naofumi</au><au>Ohtsuka, Ryoichi</au><au>Koyanagi, Mihoko</au><au>Hayashi, Shim-mo</au><au>Maronpot, Robert R.</au><au>Shibutani, Makoto</au><au>Yoshida, Toshinori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spironolactone in Combination with α-glycosyl Isoquercitrin Prevents Steatosis-related Early Hepatocarcinogenesis in Rats through the Observed NADPH Oxidase Modulation</atitle><jtitle>Toxicologic pathology</jtitle><addtitle>Toxicol Pathol</addtitle><date>2018-07</date><risdate>2018</risdate><volume>46</volume><issue>5</issue><spage>530</spage><epage>539</epage><pages>530-539</pages><issn>0192-6233</issn><eissn>1533-1601</eissn><abstract>Administration of the diuretic, spironolactone (SR), can inhibit chronic liver diseases. We determined the effects of SR alone or in combination with the antioxidant α-glycosyl isoquercitrin (AGIQ) on hyperlipidemia- and steatosis-related precancerous lesions in high-fat diet (HFD)-fed rats subjected to a two-stage hepatocarcinogenesis model. Rats were fed with control basal diet or HFD, which was administered with SR alone or in combination with an antioxidant AGIQ in drinking water. An HFD increased body weight, intra-abdominal fat (adipose) tissue weight, and plasma lipids, which were reduced by coadministration of SR and AGIQ. SR and AGIQ coadministration also reduced hepatic steatosis and preneoplastic glutathione S-transferase placental form-positive foci, in association with decrease in NADPH oxidase (NOX) subunit p22phox-positive cells and an increase in active-caspase-3-positive cells in the foci. Hepatic gene expression analysis revealed that the coadministration of SR and AGIQ altered mRNA levels of lipogenic enzymes (Scd1 and Fasn), antioxidant-related enzymes (Catalase), NOX component (P67phox), and anti-inflammatory transcriptional factor (Pparg). Our results indicated that SR in combination with AGIQ had the potential of suppressing hyperlipidemia- and steatosis-related early hepatocarcinogenesis through the reduced expression of NOX subunits.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>29843569</pmid><doi>10.1177/0192623318778508</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Toxicologic pathology, 2018-07, Vol.46 (5), p.530-539 |
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| subjects | Animals Body Weight - drug effects Diet, High-Fat Drug Therapy, Combination Fatty Liver - complications Fatty Liver - drug therapy Fatty Liver - pathology Liver Neoplasms, Experimental - etiology Liver Neoplasms, Experimental - pathology Liver Neoplasms, Experimental - prevention & control Male NADPH Oxidases - metabolism Organ Size - drug effects Oxidative Stress - drug effects Precancerous Conditions - pathology Precancerous Conditions - prevention & control Quercetin - administration & dosage Quercetin - analogs & derivatives Quercetin - therapeutic use Rats, Inbred F344 Spironolactone - administration & dosage Spironolactone - therapeutic use |
| title | Spironolactone in Combination with α-glycosyl Isoquercitrin Prevents Steatosis-related Early Hepatocarcinogenesis in Rats through the Observed NADPH Oxidase Modulation |
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