Oxidative stress induced by morphine in brain of rats fed with a protein deficient diet

Calderón-Guzmán, David; Osnaya-Brizuela, Norma; García-Álvarez, Raquel; Hernández-Garcı́a, Ernestina; Juárez-Olguı́n, Hugo

doi:10.1177/0960327109102798

Cited by 6 publications

(5 citation statements)

References 44 publications

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“…The pathway enrichment analysis identified an oxidative stress-related pathway as being modulated by morphine exposure, in agreement with previous studies [ 11 , 48 , 49 , 50 ]. Oxidative stress is an abnormal physiological process and is defined as “an imbalance between antioxidants and oxidants, resulting in the disruption of redox signaling and the corresponding molecular damage” [ 51 ].…”

Section: Discussionsupporting

confidence: 90%

Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells

Vujić

Schvartz

Furlani

et al. 2022

Cells

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Morphine, a commonly used antinociceptive drug in hospitals, is known to cross the blood-brain barrier (BBB) by first passing through brain endothelial cells. Despite its pain-relieving effect, morphine also has detrimental effects, such as the potential induction of redox imbalance in the brain. However, there is still insufficient evidence of these effects on the brain, particularly on the brain endothelial cells and the extracellular vesicles that they naturally release. Indeed, extracellular vesicles (EVs) are nanosized bioparticles produced by almost all cell types and are currently thought to reflect the physiological state of their parent cells. These vesicles have emerged as a promising source of biomarkers by indicating the functional or dysfunctional state of their parent cells and, thus, allowing a better understanding of the biological processes involved in an adverse state. However, there is very little information on the morphine effect on human brain microvascular endothelial cells (HBMECs), and even less on their released EVs. Therefore, the current study aimed at unraveling the detrimental mechanisms of morphine exposure (at 1, 10, 25, 50 and 100 µM) for 24 h on human brain microvascular endothelial cells as well as on their associated EVs. Isolation of EVs was carried out using an affinity-based method. Several orthogonal techniques (NTA, western blotting and proteomics analysis) were used to validate the EVs enrichment, quality and concentration. Data-independent mass spectrometry (DIA-MS)-based proteomics was applied in order to analyze the proteome modulations induced by morphine on HBMECs and EVs. We were able to quantify almost 5500 proteins in HBMECs and 1500 proteins in EVs, of which 256 and 148, respectively, were found to be differentially expressed in at least one condition. Pathway enrichment analysis revealed that the “cell adhesion and extracellular matrix remodeling” process and the “HIF1 pathway”, a pathway related to oxidative stress responses, were significantly modulated upon morphine exposure in HBMECs and EVs. Altogether, the combination of proteomics and bioinformatics findings highlighted shared pathways between HBMECs exposed to morphine and their released EVs. These results put forward molecular signatures of morphine-induced toxicity in HBMECs that were also carried by EVs. Therefore, EVs could potentially be regarded as a useful tool to investigate brain endothelial cells dysfunction, and to a different extent, the BBB dysfunction in patient circulation using these “signature pathways”.

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Section: Discussionsupporting

confidence: 90%

Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells

Vujić

Schvartz

Furlani

et al. 2022

Cells

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“…Morphine induces reactive oxygen species formation in various brain cells (Xu et al,2006). In addition, opiates acutely decrease glutathione levels within the brain (Goudas et al,1999; Guzman et al,2006; Calderon‐Guzman et al,2009) and suppresses glutathione peroxidase activity (Xu et al,2006). Repetitive hypoxic episodes may have also played a role; however, lower glutathione levels are more likely with chronic hypoxia (Raman et al,2005).…”

Section: Discussionmentioning

confidence: 99%

Postnatal morphine administration alters hippocampal development in rats

Traudt

Tkáč

Ennis

et al. 2011

J of Neuroscience Research

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Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg of morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo 1H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ-aminobutyric acid (GABA), taurine and myo-insotol were decreased, while glutathione, phosphoethanolamine and choline-containing compounds concentrations were increased in morphine-exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60-70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure.

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“…This effect coincides with previous studies carried out in our laboratory where the products of lipoperoxidation were found to reduce in the cerebrum after the sibutramine treatment, especially in female rats. This suggests that the effect could be attributable to the chemical structure of sibutramine which possesses certain functional groups like dimethylamine and chlorine heteroatom all found in the aromatic ring which confers to them electrophilic character that facilitates their interaction with lipidic structure of the cerebrum (Calderon et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Effect of an anorexiant on levels of 5-HIAA and GSH in brain of well-nourished and malnourished rats

Guzmán¹

2013

Afr. J. Pharm. Pharmacol.

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In this study, the effect of sibutramine and carnitine on 5-HIAA and GSH levels in brain regions of malnourished rats was analyzed. Twenty-four rats were fed with a normal protein diet (23%) and another similar group with protein starvation diet (7%). The animals of both groups were re-assigned into four groups of 6 animals per group and treated for 10 days as follows: group 1, saline solution; group 2, sibutramine (10 mg/kg); group 3, carnitine (500 mg/kg); and group 4, sibutramine (10 mg/kg) + carnitine (500 mg/kg). The animals were sacrificed at the end of treatment and their cerebrum, cortex, cerebellum and medulla oblongata were extracted to determine the levels of glucose, glutathione (GSH), lipid peroxidation (TBARS), and 5-hydroxyindole acetic acid (5-HIAA). The corporal weights of animals fed with low protein diet were significantly lower than those on normal diet. The levels of 5-HIAA, TBARS, and GSH showed significant differences due to subitramine and carnitine effects, principally in cortex than in the rest of the brain areas of rats fed with low diet. Sibutramine and carnitine alter serotonergic metabolism in the brain regions of animals subjected to low protein diets. Reduction in oxidative stress may be involved in these effects.

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Oxidative stress induced by morphine in brain of rats fed with a protein deficient diet

Cited by 6 publications

References 44 publications

Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells

Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells

Postnatal morphine administration alters hippocampal development in rats

Effect of an anorexiant on levels of 5-HIAA and GSH in brain of well-nourished and malnourished rats

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