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

Journal Title: Pharmacological Reports - Year 2009, Vol 61, Issue 5

Abstract

Mildronate (3-(2,2,2-trimethylhydrazinium) propionate), which is mostly used in cardiological 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 min of liver ischemia followed by a 30 min 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.

Authors and Affiliations

Sonata Trumbeckaite, Marius Kincius, Andrius Preidis, Monika Preidiene, Vincentas Veikutis, Vilmante Borutaite, Antanas Gulbinas

Keywords

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  • EP ID EP83333
  • DOI -
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How To Cite

Sonata Trumbeckaite, Marius Kincius, Andrius Preidis, Monika Preidiene, Vincentas Veikutis, Vilmante Borutaite, Antanas Gulbinas (2009). Effects of ischemia-reperfusion and pretreatment with mildronate on rat liver mitochondrial function.. Pharmacological Reports, 61(5), 859-869. https://europub.co.uk/articles/-A-83333