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
Related Articles
- EP ID EP83333
- DOI -
- Views 118
- Downloads 0
Characterization of motor, depressive-like and neurochemical alterations induced by a short-term rotenone administration.
Background: Rotenone exposure in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. However, several aspects remain unclear regarding the effects and the accuracy...
Differential effects of LY294002 and wortmannin on neurons and vascular endothelial cells in the rat retina.
Neuronal damage leads to capillary degeneration in an N-methyl-D-aspartate (NMDA)-induced retinal degeneration model; however, the mechanisms underlying this phenomenon are not fully understood. The phosphatidylinositol...
Effects of two isomers of DDT and their metabolite DDE on CYP1A1 and AhR function in human placental cells.
The aim of this study was to investigate the actions of two isomers of DDT (p,p'-DDT, o,p'-DDT) and DDE (p,p'-DDE, o,p'-DDE) on the human placenta. We studied the effects of DDT and its metabolite DDE on CYP1A1 activity...
Novel mechanistic and clinical implications concerning the safety of statin discontinuation.
The beneficial effects of statins have been discussed widely, and their preventative role has been confirmed in cardiovascular disorders, primary and secondary prevention settings, and in asymptomatic subjects with a hig...
Serum and intraerythrocyte antioxidant enzymes and lipid peroxides in children with migraine.
The oxidant-antioxidant balance disorders underlie a number of acute and chronic diseases of the central nervous system (CNS). It is believed that oxidative stress plays a role in the pathogenesis of migraine. The study...