Effects of N-acetylcysteine/deferoxamine, taurine and RC-3095 on respiratory chain complexes and creatine kinase activities in rat brain after sepsis.
ABSTRACT The pathogenesis of sepsis is characterized by an overwhelming systemic inflammatory response that can lead to multiple organ failure. Considering that we have recently demonstrated that mitochondrial respiratory chain and creatine kinase (CK) are altered in the brain of rats after cecal ligation and perforation (CLP) and that a combination of N-acetylcysteine/deferoxamine (NAC/DFX), taurine and RC-3095 were shown to be an effective treatment of sepsis, we investigated whether the alterations of these enzymes may be reversed by these drugs. The results demonstrated that CLP inhibited complexes I and II, and that all the treatments were able to reverse this inhibition in all brain areas studied in the present work. On the other hand, complexes III and IV were not affected by sepsis neither by any of the treatments. An increase in CK activity in brain of rats 12 h after CLP was also verified; the administration of NAC/DFX and taurine reversed the increase in CK activity in hippocampus, cerebral cortex, cerebellum and striatum. On the other hand, RC-3095 significantly decreased CK activity, when compared to sham group in all brain areas studied. This is a preliminary study which showed beneficial effects of the treatments we proposed.
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ABSTRACT: Studies have consistently reported the participation of oxidative stress, energetic metabolism impairment, and creatine kinase (CK) activity alterations in rat brain in early times in an animal model of sepsis and persist for up to 10 days. We have assessed the antioxidant effects of administration of Ebselen (Eb) e diphenyl diselenide (PhSe)2 two organoselenium compounds on brain oxidative stress, energetic metabolism, and CK activity 12, 24 h, and 10 days after sepsis by cecal ligation and perforation (CLP) in rats. Male Wistar rats underwent either sham operation or CLP and were treated with oral injection of Eb (50 mg/kg) or (PhSe)2 (50 mg/kg) or vehicle. 12, 24 h, and 10 days after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex, and cortex) were obtained and assayed for thiobarbituric acid reactive species and protein carbonyls formation, mitochondrial respiratory chain, and CK activity. We observed in the results a reduction of oxidative damage to lipids and proteins in the different cerebral structures studied and times with the administration of (PhSe)2; however, Eb seems to exert the same effect. Such changes are reflected in the assessment of mitochondrial respiratory chain complexes by reversing the decreased activity of the complex caused by the model of CLP and CK activity. Our data provide the first experimental demonstration that (PhSe)2 was able to reduce the brain dysfunction associated with CLP-induced sepsis in rats, by decreasing oxidative stress parameters mitochondrial dysfunction and CK activity in early times and in late time.Neurotoxicity Research 05/2014; · 2.87 Impact Factor
- Neurological Sciences 04/2013; · 1.41 Impact Factor
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ABSTRACT: In the present study, we investigated whether sepsis induced by cecal ligation and puncture (CLP) modifies Na(+), K(+)-ATPase activity, mRNA expression, and cerebral edema in hippocampus and cerebral cortex of rats and if antioxidant (ATX) treatment prevented the alterations induced by sepsis. Rats were subjected to CLP and were divided into three groups: sham; CLP-rats were subjected to CLP without any further treatment; and ATX-CLP plus administration of N-acetylcysteine plus deferoxamine. Several times (6, 12, and 24) after CLP or sham operation, the rats were killed and hippocampus and cerebral cortex were isolated. Na(+), K(+)-ATPase activity was inhibited in the hippocampus 24 h after sepsis, and ATX treatment was not able to prevent this inhibition. The Na(+), K(+)-ATPase activity also was inhibited in cerebral cortex 6, 12, and 24 h after sepsis. No differences on Na(+), K(+)-ATPase catalytic subunit mRNA levels were found in the hippocampus and cerebral cortex after sepsis. ATX treatment prevents Na(+), K(+)-ATPase inhibition only in the cerebral cortex. Na(+), K(+)-ATPase inhibition was not associated to increase brain water content. In conclusion, the present study demonstrated that sepsis induced by CLP inhibits Na(+), K(+)-ATPase activity in a mechanism dependent on oxidative stress, but this is not associated to increase brain water content.Molecular Neurobiology 07/2012; 46(2):467-74. · 5.47 Impact Factor