Effects of ischemia-reperfusion and pretreatment with mildronate on rat liver mitochondrial function

被引:6
作者
Trumbeckaite, Sonata [1 ]
Kincius, Marius [1 ]
Preidis, Andrius [1 ]
Preidiene, Monika [1 ]
Veikutis, Vincentas [1 ]
Borutaite, Vilmante [1 ]
Gulbinas, Antanas [1 ]
机构
[1] Kaunas Univ Med, Inst Biomed Res, LT-50009 Kaunas 7, Lithuania
关键词
liver mitochondria; mildronate; ischemia; reperfusion; aspartate aminotransferase; alanine aminotransferase; BUTYROBETAINE HYDROXYLASE INHIBITOR; FATTY-ACID OXIDATION; INJURY; HEART; CARDIOPROTECTION; TRANSPLANTATION; MECHANISMS; STEATOSIS; STRESS; MET-88;
D O I
10.1016/S1734-1140(09)70142-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mildronate (3-(2,2,2-trimethylhydrazinium) propronate), which is mostly used in carchological practice and is considered an anti-ischemic drug, was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation Recently it was shown that the mitochondrial respiratory chain may also be a target for mildronate action In this study, we aimed to investigate whether mildronate can protect the liver against a 90-min normothermic ischemia/30-min reperfusion-induced mitochondrial dysfunction Rats were pre-treated for one or two weeks with mildronate (100 mg/kg/day or 200 mg/kg/day) or Ringer solution and subjected to ischemia/reperfusion We found that ischemia/reperfusion caused a decrease in mitochondrial State 3 respiration rate and in the respiratory control index (RCI), and an increase in State 2 respiration rate with succinate, glutamate + malate and palmitoyl-L-carnitine + malate. One or two weeks of pre-treatment of rats with different doses of mildronate did not reduce the ischemia/reperfusion-induced decrease in the State 3 respiration rate or RCI; however, a one week pre-treatment slightly diminished the increase in the State 2 respiration rate with glutamate + malate substrates. The leakage of the liver enzymes, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase, was similar in both the untreated and pre-treated with mildronate groups No steatotic livers were observed in any experimental groups after mildronate pre-treatment In conclusion, 90 mm of liver ischemia followed by a 30 mm reperfusion has a deleterious effect on rat liver mitochondrial function Mildronate pre-treatment of rats at doses of 100 or 200 mg/kg/day for one or two weeks did not prevent ischemia/reperfusion-induced mitochondrial dysfunction and liver injury.
引用
收藏
页码:859 / 869
页数:11
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