We investigated the changes in redox state and protein expression in selected parts of the rat brain induced by a 4 week administration of morphine (10 mg/kg/day). We found a significant reduction in lipid peroxidation that mostly persisted for 1 week after morphine withdrawal. Morphine treatment led to a significant increase in complex II in the cerebral cortex (Crt), which was accompanied by increased protein carbonylation, in contrast to the other brain regions studied. Glutathione levels were altered differently in the different brain regions after morphine treatment. Using label-free quantitative proteomic analysis, we found some specific changes in protein expression profiles in the Crt, hippocampus, striatum, and cerebellum on the day after morphine withdrawal and 1 week later. A common feature was the upregulation of anti-apoptotic proteins and dysregulation of the extracellular matrix. Our results indicate that the tested protocol of morphine administration has no significant toxic effect on the rat brain. On the contrary, it led to a decrease in lipid peroxidation and activation of anti-apoptotic proteins. Furthermore, our data suggest that long-term treatment with morphine acts specifically on different brain regions and that a 1 week drug withdrawal is not sufficient to normalize cellular redox state and protein levels.

• Klíčová slova
• brain, morphine, oxidative stress, proteomics, withdrawal,
• Publikační typ
• časopisecké články MeSH

Hypertension, dyslipidemia, and insulin resistance in the spontaneously hypertensive rat (SHR) can be alleviated by rescuing CD36 fatty acid translocase. The present study investigated whether transgenic rescue of CD36 in SHR could affect mitochondrial function and activity of selected metabolic enzymes in the heart. These analyses were conducted on ventricular preparations derived from SHR and from transgenic strain SHR-Cd36 that expresses a functional wild-type CD36. Our respirometric measurements revealed that mitochondria isolated from the left ventricles exhibited two times higher respiratory activity than those isolated from the right ventricles. Whereas, we did not observe any significant changes in functioning of the mitochondrial respiratory system between both rat strains, enzyme activities of total hexokinase, and both mitochondrial and total malate dehydrogenase were markedly decreased in the left ventricles of transgenic rats, compared to SHR. We also detected downregulated expression of the succinate dehydrogenase subunit SdhB (complex II) and 70 kDa peroxisomal membrane protein in the left ventricles of SHR-Cd36. These data indicate that CD36 may affect in a unique fashion metabolic substrate flexibility of the left and right ventricles.

• Klíčová slova
• CD36, Heart, Left and right ventricles, Mitochondria, OXPHOS, SHR,
• MeSH
• ABC transportéry genetika   metabolismus   MeSH
• antigeny CD36 genetika   metabolismus   MeSH
• exprese genu MeSH
• hexokinasa genetika   metabolismus   MeSH
• hypertenze enzymologie   genetika   patofyziologie   MeSH
• inzulinová rezistence MeSH
• kardiomyocyty enzymologie   patologie   MeSH
• krysa rodu Rattus MeSH
• malátdehydrogenasa genetika   metabolismus   MeSH
• mitochondrie enzymologie   patologie   MeSH
• oxidativní fosforylace MeSH
• potkani inbrední SHR MeSH
• potkani transgenní MeSH
• primární buněčná kultura MeSH
• regulace genové exprese MeSH
• spotřeba kyslíku genetika   MeSH
• srdeční komory enzymologie   patologie   MeSH
• sukcinátdehydrogenasa genetika   metabolismus   MeSH
• transgeny * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportéry MeSH
• Abcd3 protein, rat MeSH Prohlížeč
• antigeny CD36 MeSH
• hexokinasa MeSH
• malátdehydrogenasa MeSH
• sukcinátdehydrogenasa MeSH

Morphine exhibits important pharmacological effects for which it has been used in medical practice for quite a long time. However, it has a high addictive potential and can be abused. Long-term use of this drug can be connected with some pathological consequences including neurotoxicity and neuronal dysfunction, hepatotoxicity, kidney dysfunction, oxidative stress and apoptosis. Therefore, most studies examining the impact of morphine have been aimed at determining the effects induced by chronic morphine exposure in the brain, liver, cardiovascular system and macrophages. It appears that different tissues may respond to morphine diversely and are distinctly susceptible to oxidative stress and subsequent oxidative damage of biomolecules. Importantly, production of reactive oxygen/nitrogen species induced by morphine, which have been observed under different experimental conditions, can contribute to some pathological processes, degenerative diseases and organ dysfunctions occurring in morphine abusers or morphine-treated patients. This review attempts to provide insights into the possible relationship between morphine actions and oxidative stress.

• Klíčová slova
• Morphine, oxidative stress, reactive oxygen and nitrogen species.,
• Publikační typ
• časopisecké články MeSH