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Article: Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury

TitleInhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury
Authors
KeywordsInflammation
Lipid peroxidation
Liver injury
Nitric oxide
Oxidative stress
Issue Date2006
PublisherHistology and Histopathology. The Journal's web site is located at http://www.hh.um.es
Citation
Histology And Histopathology, 2006, v. 21 n. 10-12, p. 1157-1165 How to Cite?
AbstractThe exact functional role of nitric oxide (NO) in liver injury is currently a source of controversy. NO is enzymatically synthesized by nitric oxide synthase (NOS). In this study, we assessed the role of inducible NOS (iNOS) in carbon tetrachloride (CCl 4)-induced acute liver injury using inhibitors of iNOS, and an NO donor. Adult ICR mice were injected with CCl 4 with or without the iNOS inhibitors (5-methylisothiourea hemisulfate [SMT] and 1-N 6-(1-iminoethyl)-lysine [L-NIL]) and an NO donor (Sodium Nitroprusside [SNP]). Blood and liver tissues were collected for analysis. Immunohistochemistry (IHC), serum alanine aminotransferase (ALT), serum total 8-isoprostane analysis, RT-PCR, Western Blotting (WB) and EMSA were done. Our results showed increased levels of ALT, necrosis, total 8-isoprostane and nitrotyrosine after CCl 4 administration. iNOS inhibitors and SNP abrogated these effects but the effect was more pronounced with SMT and L-NIL. RT-PCR, WB and IHC in CCl 4-treated mice demonstrated upregulation of TNF-α, iNOS, and COX-2. The administration of iNOS inhibitors with CCl 4 diminished the expression of these proinflammatory mediators. NF-κB was also upregulated in CCl 4-treated mice and was reversed in mice pretreated wil iNOS inhibitors. SNP pretreated mice also showed a lower expression of COX-2 when compared with CCl 4 treated mice but TNF-α, iNOS and NF-κB activity were unaffected. We propose that a high level of nitric oxide is associated with CCl 4-induced acute liver injury and the liver injury can be ameliorated by decreasing the NO level with iNOS inhibitors and an NO donor with the former more effective in reducing CCl 4-induced liver injury.
Persistent Identifierhttp://hdl.handle.net/10722/67881
ISSN
2015 Impact Factor: 1.875
2015 SCImago Journal Rankings: 0.805
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTipoe, GLen_HK
dc.contributor.authorLeung, TMen_HK
dc.contributor.authorLiong, Een_HK
dc.contributor.authorSo, Hen_HK
dc.contributor.authorLeung, KMen_HK
dc.contributor.authorLau, TYHen_HK
dc.contributor.authorTom, WMen_HK
dc.contributor.authorFung, MLen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorNanji, AAen_HK
dc.date.accessioned2010-09-06T05:59:07Z-
dc.date.available2010-09-06T05:59:07Z-
dc.date.issued2006en_HK
dc.identifier.citationHistology And Histopathology, 2006, v. 21 n. 10-12, p. 1157-1165en_HK
dc.identifier.issn0213-3911en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67881-
dc.description.abstractThe exact functional role of nitric oxide (NO) in liver injury is currently a source of controversy. NO is enzymatically synthesized by nitric oxide synthase (NOS). In this study, we assessed the role of inducible NOS (iNOS) in carbon tetrachloride (CCl 4)-induced acute liver injury using inhibitors of iNOS, and an NO donor. Adult ICR mice were injected with CCl 4 with or without the iNOS inhibitors (5-methylisothiourea hemisulfate [SMT] and 1-N 6-(1-iminoethyl)-lysine [L-NIL]) and an NO donor (Sodium Nitroprusside [SNP]). Blood and liver tissues were collected for analysis. Immunohistochemistry (IHC), serum alanine aminotransferase (ALT), serum total 8-isoprostane analysis, RT-PCR, Western Blotting (WB) and EMSA were done. Our results showed increased levels of ALT, necrosis, total 8-isoprostane and nitrotyrosine after CCl 4 administration. iNOS inhibitors and SNP abrogated these effects but the effect was more pronounced with SMT and L-NIL. RT-PCR, WB and IHC in CCl 4-treated mice demonstrated upregulation of TNF-α, iNOS, and COX-2. The administration of iNOS inhibitors with CCl 4 diminished the expression of these proinflammatory mediators. NF-κB was also upregulated in CCl 4-treated mice and was reversed in mice pretreated wil iNOS inhibitors. SNP pretreated mice also showed a lower expression of COX-2 when compared with CCl 4 treated mice but TNF-α, iNOS and NF-κB activity were unaffected. We propose that a high level of nitric oxide is associated with CCl 4-induced acute liver injury and the liver injury can be ameliorated by decreasing the NO level with iNOS inhibitors and an NO donor with the former more effective in reducing CCl 4-induced liver injury.en_HK
dc.languageengen_HK
dc.publisherHistology and Histopathology. The Journal's web site is located at http://www.hh.um.esen_HK
dc.relation.ispartofHistology and Histopathologyen_HK
dc.subjectInflammationen_HK
dc.subjectLipid peroxidationen_HK
dc.subjectLiver injuryen_HK
dc.subjectNitric oxideen_HK
dc.subjectOxidative stressen_HK
dc.titleInhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injuryen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0213-3911&volume=21&issue=11&spage=1157&epage=1165&date=2006&atitle=Inhibitors+of+inducible+nitric+oxide+(NO)+synthase+are+more+effective+than+an+NO+donor+in+reducing+carbon-tetrachloride+induced+acute+liver+injuryen_HK
dc.identifier.emailTipoe, GL: tgeorge@hkucc.hku.hken_HK
dc.identifier.emailTom, WM: wmtoma@hkucc.hku.hken_HK
dc.identifier.emailFung, ML: fungml@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityTipoe, GL=rp00371en_HK
dc.identifier.authorityTom, WM=rp00237en_HK
dc.identifier.authorityFung, ML=rp00433en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid16874658-
dc.identifier.scopuseid_2-s2.0-33750299548en_HK
dc.identifier.hkuros117709en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33750299548&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue10-12en_HK
dc.identifier.spage1157en_HK
dc.identifier.epage1165en_HK
dc.identifier.isiWOS:000239239800003-
dc.publisher.placeSpainen_HK
dc.identifier.scopusauthoridTipoe, GL=7003550610en_HK
dc.identifier.scopusauthoridLeung, TM=7202110149en_HK
dc.identifier.scopusauthoridLiong, E=6602732210en_HK
dc.identifier.scopusauthoridSo, H=14068993500en_HK
dc.identifier.scopusauthoridLeung, KM=7401860685en_HK
dc.identifier.scopusauthoridLau, TYH=26323763000en_HK
dc.identifier.scopusauthoridTom, WM=7003709519en_HK
dc.identifier.scopusauthoridFung, ML=7101955092en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridNanji, AA=35885060300en_HK

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