Tkachova O. Rat liver energy and prooxidant-antioxidant state under hypothermic storage and following reperfusion

The thesis is dedicated to the problem of liver hypothermic storage. The aim of the study was to improve the preservation protocol using in vivo pretreatment of animals with biological active substances and modification of the preservation solution. It was shown that animal pretreatment with fetal tissue cytosol sustained ATP level in liver and stimulated the carbohydrates turnover in cytoplasm. It resulted in substrate accumulation and increase in mitochondrial respiratory rates after liver hypothermic storage. This work demonstrates that fetal tissue cytosol pretreatment is a promising approach for organ preservation. Substitution of albumin for PEG-8000 and tris-HCl buffer for phosphate buffer had equally protective effect on the energetic and prooxidant-antioxidant state during liver hypothermic storage and normothermic reperfusion. Thus PEG-8000 and phosphate buffer may be recommended as alternative compounds of preservation media. It was established that reversible uncoupling of oxidative phosphorylation caused by dinitrophenol presence in the preservation solution decreased TBAR-product formation and delayed impairment of antioxidant defense system. This was accompanied by ATP level maintenance during hypothermic storage and subsequent normothermic reperfusion. Combination of animal pretreatment with fetal tissue cytosol and supplementation of preservation solution with dinitrophenol had additive effect.