Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade
Lupeol, a triterpene, possesses numerous pharmacological activities, including anti-malarial, anti-arthritic and anti-carcinogenic properties. The present study was conducted to explore the hepatoprotective potential of lupeol against acetaminophen (AAP)-induced hepatotoxicity in Wistar rats. Rats w...
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| Veröffentlicht in: | Life sciences (1973) 2012-04, Vol.90 (15-16), p.561-570 |
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| creator | Kumari, Archana Kakkar, Poonam |
| description | Lupeol, a triterpene, possesses numerous pharmacological activities, including anti-malarial, anti-arthritic and anti-carcinogenic properties. The present study was conducted to explore the hepatoprotective potential of lupeol against acetaminophen (AAP)-induced hepatotoxicity in Wistar rats.
Rats were given a prophylactic treatment of lupeol (150mg/kg body weight, p.o., for 30 consecutive days) with a co-administration of AAP (1g/kg body weight). The modulatory effects of lupeol on AAP-induced hepatotoxicity were investigated by assaying oxidative stress biomarkers, serum liver toxicity markers, pro/anti apoptotic proteins, DNA fragmentation and by the histopathological examination of the liver.
Lupeol significantly prevented hepatic damage as evident from the histopathological studies and significant decline in serum trans-aminases. The alterations in cellular redox status (p |
| doi_str_mv | 10.1016/j.lfs.2012.01.012 |
| format | Article |
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Rats were given a prophylactic treatment of lupeol (150mg/kg body weight, p.o., for 30 consecutive days) with a co-administration of AAP (1g/kg body weight). The modulatory effects of lupeol on AAP-induced hepatotoxicity were investigated by assaying oxidative stress biomarkers, serum liver toxicity markers, pro/anti apoptotic proteins, DNA fragmentation and by the histopathological examination of the liver.
Lupeol significantly prevented hepatic damage as evident from the histopathological studies and significant decline in serum trans-aminases. The alterations in cellular redox status (p<0.01) and antioxidant enzyme activities together with the enhanced lipid peroxidation and protein carbonyl levels were also observed in the AAP-treated rats. In addition, significant ROS generation and mitochondrial depolarization were observed in this group. Co-administration of lupeol significantly decreased the level of serum transaminases, MDA and protein carbonyl content. It also prevented ROS generation and mitochondrial depolarization. Furthermore, lupeol enhanced the mitochondrial antioxidant and redox status and inhibited DNA damage and cell death by preventing the downregulation of Bcl-2, upregulation of Bax, release of cytochrome c and the activation of caspase 9/3.
The conclusion of this study is that lupeol when co-administered with AAP effectively reduces oxidative stress and prevents AAP-induced hepatotoxicity by inhibiting critical control points of apoptosis.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2012.01.012</identifier><identifier>PMID: 22326499</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Acetaminophen ; Acetaminophen - toxicity ; Analysis of Variance ; Animals ; anticarcinogenic activity ; antimalarials ; antioxidants ; apoptosis ; bcl-2-Associated X Protein ; biomarkers ; Biomarkers - metabolism ; blood serum ; Blotting, Western ; body weight ; Case-Control Studies ; caspases ; Catalase - metabolism ; cytochrome c ; DNA damage ; DNA Fragmentation ; enzyme activity ; Flow Cytometry ; Glutathione Peroxidase - metabolism ; Glutathione Reductase - metabolism ; Glutathione Transferase - metabolism ; Hepatotoxicity ; histopathology ; In Situ Nick-End Labeling ; lipid peroxidation ; liver ; Liver - drug effects ; Liver - metabolism ; Lupeol ; Male ; Membrane Potential, Mitochondrial - drug effects ; Mitochondria - metabolism ; Mitochondria - physiology ; Mitochondrial depolarization ; Molecular Structure ; Oxidative stress ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; Pentacyclic Triterpenes - chemistry ; Pentacyclic Triterpenes - pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; Rats ; Rats, Wistar ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Superoxide Dismutase - metabolism ; transaminases</subject><ispartof>Life sciences (1973), 2012-04, Vol.90 (15-16), p.561-570</ispartof><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-4f241d438fc9c982907007bc907a91ff62c6a72245a5e520ef75c2126583d7d43</citedby><cites>FETCH-LOGICAL-c410t-4f241d438fc9c982907007bc907a91ff62c6a72245a5e520ef75c2126583d7d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2012.01.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22326499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumari, Archana</creatorcontrib><creatorcontrib>Kakkar, Poonam</creatorcontrib><title>Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Lupeol, a triterpene, possesses numerous pharmacological activities, including anti-malarial, anti-arthritic and anti-carcinogenic properties. The present study was conducted to explore the hepatoprotective potential of lupeol against acetaminophen (AAP)-induced hepatotoxicity in Wistar rats.
Rats were given a prophylactic treatment of lupeol (150mg/kg body weight, p.o., for 30 consecutive days) with a co-administration of AAP (1g/kg body weight). The modulatory effects of lupeol on AAP-induced hepatotoxicity were investigated by assaying oxidative stress biomarkers, serum liver toxicity markers, pro/anti apoptotic proteins, DNA fragmentation and by the histopathological examination of the liver.
Lupeol significantly prevented hepatic damage as evident from the histopathological studies and significant decline in serum trans-aminases. The alterations in cellular redox status (p<0.01) and antioxidant enzyme activities together with the enhanced lipid peroxidation and protein carbonyl levels were also observed in the AAP-treated rats. In addition, significant ROS generation and mitochondrial depolarization were observed in this group. Co-administration of lupeol significantly decreased the level of serum transaminases, MDA and protein carbonyl content. It also prevented ROS generation and mitochondrial depolarization. Furthermore, lupeol enhanced the mitochondrial antioxidant and redox status and inhibited DNA damage and cell death by preventing the downregulation of Bcl-2, upregulation of Bax, release of cytochrome c and the activation of caspase 9/3.
The conclusion of this study is that lupeol when co-administered with AAP effectively reduces oxidative stress and prevents AAP-induced hepatotoxicity by inhibiting critical control points of apoptosis.</description><subject>Acetaminophen</subject><subject>Acetaminophen - toxicity</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>anticarcinogenic activity</subject><subject>antimalarials</subject><subject>antioxidants</subject><subject>apoptosis</subject><subject>bcl-2-Associated X Protein</subject><subject>biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>blood serum</subject><subject>Blotting, Western</subject><subject>body weight</subject><subject>Case-Control Studies</subject><subject>caspases</subject><subject>Catalase - metabolism</subject><subject>cytochrome c</subject><subject>DNA damage</subject><subject>DNA Fragmentation</subject><subject>enzyme activity</subject><subject>Flow Cytometry</subject><subject>Glutathione Peroxidase - metabolism</subject><subject>Glutathione Reductase - metabolism</subject><subject>Glutathione Transferase - metabolism</subject><subject>Hepatotoxicity</subject><subject>histopathology</subject><subject>In Situ Nick-End Labeling</subject><subject>lipid peroxidation</subject><subject>liver</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Lupeol</subject><subject>Male</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - physiology</subject><subject>Mitochondrial depolarization</subject><subject>Molecular Structure</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Pentacyclic Triterpenes - chemistry</subject><subject>Pentacyclic Triterpenes - pharmacology</subject><subject>Proto-Oncogene Proteins c-bcl-2</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Superoxide Dismutase - metabolism</subject><subject>transaminases</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc-O0zAQxiMEYsvCA3ABH_eS7tiJk0ac2BX_pEocYM_W1J60rhI72E60fQ8eGFddOCLNaC6_79PMfEXxlsOaA29uj-uhj2sBXKyB5xLPihXftF0JTcWfFysAUZeVAHlVvIrxCABSttXL4kqISjR1162K39t5Ij-wKdBCLkWGmhKO1vnpQK60zsyaDLOOLXbx7EATJp_8o9U2ndjuxHBIFKzbs3QgdoePt3d6KAVDZ1imDCa7EIspUIzlSMZiynajTV4fvDPB4sCi3Tsczh4ao0ZDr4sXPQ6R3jzN6-Lh86ef91_L7fcv3-4_bktdc0hl3Yuam7ra9LrT3UZ00AK0O50ndrzvG6EbbIWoJUqSAqhvpRZcNHJTmTYLr4ubi-8U_K-ZYlKjjZqGAR35OSpeNW294W0jM8ovqA4-xkC9moIdMZwUB3UOQx1VDkOdw1DAc4msefdkP-_y6f8Uf7-fgfcXoEevcB9sVA8_soOE3AIqnokPF4LyGxZLQUVtyeVIbCCdlPH2Pwv8AWyjpaE</recordid><startdate>20120420</startdate><enddate>20120420</enddate><creator>Kumari, Archana</creator><creator>Kakkar, Poonam</creator><general>Elsevier Inc</general><scope>FBQ</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>7U7</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope></search><sort><creationdate>20120420</creationdate><title>Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade</title><author>Kumari, Archana ; Kakkar, Poonam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-4f241d438fc9c982907007bc907a91ff62c6a72245a5e520ef75c2126583d7d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acetaminophen</topic><topic>Acetaminophen - toxicity</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>anticarcinogenic activity</topic><topic>antimalarials</topic><topic>antioxidants</topic><topic>apoptosis</topic><topic>bcl-2-Associated X Protein</topic><topic>biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>blood serum</topic><topic>Blotting, Western</topic><topic>body weight</topic><topic>Case-Control Studies</topic><topic>caspases</topic><topic>Catalase - metabolism</topic><topic>cytochrome c</topic><topic>DNA damage</topic><topic>DNA Fragmentation</topic><topic>enzyme activity</topic><topic>Flow Cytometry</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>Glutathione Reductase - metabolism</topic><topic>Glutathione Transferase - metabolism</topic><topic>Hepatotoxicity</topic><topic>histopathology</topic><topic>In Situ Nick-End Labeling</topic><topic>lipid peroxidation</topic><topic>liver</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Lupeol</topic><topic>Male</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - physiology</topic><topic>Mitochondrial depolarization</topic><topic>Molecular Structure</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>Pentacyclic Triterpenes - chemistry</topic><topic>Pentacyclic Triterpenes - pharmacology</topic><topic>Proto-Oncogene Proteins c-bcl-2</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Superoxide Dismutase - metabolism</topic><topic>transaminases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumari, Archana</creatorcontrib><creatorcontrib>Kakkar, Poonam</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumari, Archana</au><au>Kakkar, Poonam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2012-04-20</date><risdate>2012</risdate><volume>90</volume><issue>15-16</issue><spage>561</spage><epage>570</epage><pages>561-570</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Lupeol, a triterpene, possesses numerous pharmacological activities, including anti-malarial, anti-arthritic and anti-carcinogenic properties. The present study was conducted to explore the hepatoprotective potential of lupeol against acetaminophen (AAP)-induced hepatotoxicity in Wistar rats.
Rats were given a prophylactic treatment of lupeol (150mg/kg body weight, p.o., for 30 consecutive days) with a co-administration of AAP (1g/kg body weight). The modulatory effects of lupeol on AAP-induced hepatotoxicity were investigated by assaying oxidative stress biomarkers, serum liver toxicity markers, pro/anti apoptotic proteins, DNA fragmentation and by the histopathological examination of the liver.
Lupeol significantly prevented hepatic damage as evident from the histopathological studies and significant decline in serum trans-aminases. The alterations in cellular redox status (p<0.01) and antioxidant enzyme activities together with the enhanced lipid peroxidation and protein carbonyl levels were also observed in the AAP-treated rats. In addition, significant ROS generation and mitochondrial depolarization were observed in this group. Co-administration of lupeol significantly decreased the level of serum transaminases, MDA and protein carbonyl content. It also prevented ROS generation and mitochondrial depolarization. Furthermore, lupeol enhanced the mitochondrial antioxidant and redox status and inhibited DNA damage and cell death by preventing the downregulation of Bcl-2, upregulation of Bax, release of cytochrome c and the activation of caspase 9/3.
The conclusion of this study is that lupeol when co-administered with AAP effectively reduces oxidative stress and prevents AAP-induced hepatotoxicity by inhibiting critical control points of apoptosis.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>22326499</pmid><doi>10.1016/j.lfs.2012.01.012</doi><tpages>10</tpages></addata></record> |
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| ispartof | Life sciences (1973), 2012-04, Vol.90 (15-16), p.561-570 |
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| subjects | Acetaminophen Acetaminophen - toxicity Analysis of Variance Animals anticarcinogenic activity antimalarials antioxidants apoptosis bcl-2-Associated X Protein biomarkers Biomarkers - metabolism blood serum Blotting, Western body weight Case-Control Studies caspases Catalase - metabolism cytochrome c DNA damage DNA Fragmentation enzyme activity Flow Cytometry Glutathione Peroxidase - metabolism Glutathione Reductase - metabolism Glutathione Transferase - metabolism Hepatotoxicity histopathology In Situ Nick-End Labeling lipid peroxidation liver Liver - drug effects Liver - metabolism Lupeol Male Membrane Potential, Mitochondrial - drug effects Mitochondria - metabolism Mitochondria - physiology Mitochondrial depolarization Molecular Structure Oxidative stress Oxidative Stress - drug effects Oxidative Stress - physiology Pentacyclic Triterpenes - chemistry Pentacyclic Triterpenes - pharmacology Proto-Oncogene Proteins c-bcl-2 Rats Rats, Wistar Signal Transduction - drug effects Signal Transduction - physiology Superoxide Dismutase - metabolism transaminases |
| title | Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade |
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