TY - JOUR
T1 - Sodium nitrite attenuates hepatic Ischemia-Reperfusion injury in rats
AU - Choi, Eun Kyung
AU - Jung, Hoon
AU - Kim, Kyung Ju
AU - Kang, So Jeong
AU - Kim, Hyun Jeong
AU - Lim, Jung A.
AU - Kwak, Kyung Hwa
AU - Lim, Dong Gun
N1 - Publisher Copyright:
© Başkent University 2019 Printed in Turkey. All Rights Reserved.
PY - 2019/6
Y1 - 2019/6
N2 - Objectives: 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-1Himidazolyl- 1-oxy-3oxide (C-PTIO), a nitric oxide scavenger, and allopurinol, a xanthine oxidoreductase inhibitor. Materials and Methods: 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 ischemiareperfusion 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 admi nistration. Blood aspartate aminotransferase, alanine aminotransferase, hepatic tissue malondialdehyde, histologic changes, and expression of mitogen-activated protein kinase family members were evaluated. Results: 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-reperfusioninduced c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation. Conclusions: 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.
AB - Objectives: 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-1Himidazolyl- 1-oxy-3oxide (C-PTIO), a nitric oxide scavenger, and allopurinol, a xanthine oxidoreductase inhibitor. Materials and Methods: 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 ischemiareperfusion 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 admi nistration. Blood aspartate aminotransferase, alanine aminotransferase, hepatic tissue malondialdehyde, histologic changes, and expression of mitogen-activated protein kinase family members were evaluated. Results: 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-reperfusioninduced c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation. Conclusions: 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.
KW - Liver transplantation
KW - Nitric oxide
KW - Xanthine oxidoreductase
UR - http://www.scopus.com/inward/record.url?scp=85067298388&partnerID=8YFLogxK
U2 - 10.6002/ect.2018.0169
DO - 10.6002/ect.2018.0169
M3 - Article
C2 - 30602366
AN - SCOPUS:85067298388
SN - 1304-0855
VL - 17
SP - 348
EP - 354
JO - Experimental and Clinical Transplantation
JF - Experimental and Clinical Transplantation
IS - 3
ER -