Abstract
Nitrite as an alternative source of nitric oxide has been proposed, as it can mediate the protective response in the presence of ischemia or hypoxic conditions and inorganic nitrite can be reduced to nitric oxide by xanthine oxidoreductase. Here, we investigated whether pretreatment with sodium nitrite can attenuate liver damage in hepatic ischemia-reperfusion injury and identified the possible mechanism of nitrite reduction using 2-(4-carboxyphenyl)-4,5dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3oxide (C-PTIO), a nitric oxide scavenger, and allopurinol, a xanthine oxidoreductase inhibitor. In experiment 1, 30 male Sprague-Dawley rats were divided into 5 groups: (1) sham-operated; (2) hepatic ischemia-reperfusion injury; and (3-5) sodium nitrite administered intra-peritoneally 30 minutes before ischemia at 2.5, 25, and 250 μmol/kg, respectively. In experiment 2, 24 male Sprague-Dawley rats were divided into 4 groups: (1) hepatic ischemia-reperfusion injury; (2) sodium nitrite + hepatic ischemia-reperfusion injury; (3) C-PTIO + sodium nitrite + hepatic ischemia-reperfusion injury; and (4) allopurinol + sodium nitrite + hepatic ischemia-reperfusion injury. Sodium nitrite (25 μmol/kg) was then administered 30 minutes before hepatic ischemia, and C-PTIO or allopurinol was administered 5 minutes before sodium nitrite administration. Blood aspartate aminotransferase, alanine aminotransferase, hepatic tissue malondialdehyde, histologic changes, and expression of mitogen-activated protein kinase family members were evaluated. Sodium nitrite limited serum elevation of alanine aminotransferase and aspartate aminotransferase induced by hepatic ischemia-reperfusion with a peak effect occurring at 25 μmol/kg sodium nitrite. Pre-treatment with allopurinol abolished the protective effect of sodium nitrite, and C-PTIO treatment attenuated the hepatoprotection of sodium nitrite in rats with hepatic ischemia-reperfusion injury. Liver malondialdehyde activity after ischemia-reperfusion decreased in sodium nitrite-treated rats. Sodium nitrite also prevented hepatic ischemia-reperfusion-induced c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation. Exogenous sodium nitrite had protective effects against hepatic ischemia-reperfusion injury. Catalytic reduction to nitric oxide and attenuation of hepatic ischemia-reperfusion is dependent on xanthine oxidoreductase.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
