Abstract
Transient hepatic ischemia can cause significant liver injury. A central and early event in ischemia/reperfusion (I/R) injury is the impairment of mitochondria. The phospholipid cardiolipin (CL) is required for efficient mitochondrial function. The aim of this study was to analyze composition, content, and oxidation of CL in dependence of I/R stress. Therefore, we exposed rat livers to 20 min ischemia by interrupting the perfusion with Krebs-Ringer solution in situ. Tissue histology as well as increased activities of LDH, GLDH, and ASAT analysed in the efflux after 50 min reperfusion indicated impairment of the liver. For the analysis of local CL distribution the liver homogenate was separated according to density into 11 fractions. The fractions displayed different contents of CL and citrate synthase peaking at density of about 1.07 g/cm3. Among the fractions, the distribution of molecular CL species significantly differed. I/R caused loss of about 30 % CL and 17 % citrate synthase activity. Further, I/R shifted the CL and citrate synthase activity profile toward lower densities. Oxidized CL was exclusively found in fractions with high CL and citrate synthase content after I/R stress. I/R treatment caused significant changes in the distribution of molecular CL species. Our data demonstrate that I/R causes significant decrease in CL content and increase of oxidized CL that may be of impact for impairment of mitochondrial function by I/R. These results lead to the suggestion that strategies supporting anti-oxidative defence and CL synthesis may be beneficial to reduce I/R injury of the liver.
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We gratefully acknowledge Prof. Siegfried Kropf for the statistical analysis as well as Mrs. Daniela Peter, Mrs. Silke Niemann, Mrs. Elke Wölfel, and Mrs. Leona Bück for excellent technical assistance.
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Martens, JC., Keilhoff, G., Halangk, W. et al. Lipidomic analysis of molecular cardiolipin species in livers exposed to ischemia/reperfusion. Mol Cell Biochem 400, 253–263 (2015). https://doi.org/10.1007/s11010-014-2282-1
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DOI: https://doi.org/10.1007/s11010-014-2282-1