作者: Jin Hyen Baek , Xiaoyuan Zhang , Matthew C. Williams , Wayne Hicks , Paul W. Buehler
DOI: 10.1016/J.TOX.2015.04.007
关键词: Methemoglobinemia 、 Pharmacology 、 Lipid peroxidation 、 Hemoglobin 、 Toxicity 、 Oxidative stress 、 Sodium nitrite 、 Extracellular 、 Kidney 、 Immunology 、 Chemistry
摘要: Methemoglobin-forming drugs, such as sodium nitrite (NaNO2), may exacerbate oxidative toxicity under certain chronic or acute hemolytic settings. In this study, we evaluated markers of renal stress and injury in guinea pigs exposed to extracellular hemoglobin (Hb) followed by NaNO2 at doses sufficient simulate clinically relevant methemoglobinemia. induced rapid extensive oxidation plasma Hb model. This was accompanied increased expression the response effectors nuclear factor erythroid 2-derived-factor 2 (Nrf-2) heme oxygenase-1 (HO-1), elevated non-heme iron deposition, lipid peroxidation, interstitial inflammatory cell activation, tubular kidney injury-1 marker (KIM-1) liver-fatty acid binding protein (L-FABP), podocyte injury, death. Importantly, these indicators were minimal absent following infusion alone. Together, results suggest that exposure settings associated with potentiate via processes are independent erythrocyte