Meloxicam-loaded nanocapsules as an alternative to improve memory decline in an Alzheimer’s disease model in mice: involvement of Na+, K+-ATPase

Ianiski, Francine R.; Alves, Catiane B.; Ferreira, Carla Fontoura; Rech, Virgínia Cielo; Savegnago, Lucielli; Wilhelm, Ethel A.

doi:10.1007/s11011-016-9812-3

Cited by 23 publications

(11 citation statements)

References 60 publications

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“…Considering that an association between brain degenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's diseases, with oxidative stress exists [46], meloxicam could be a promising treatment for them. In fact, an improvement in symptoms of Alzheimer's disease has been reported in a mouse model with this drug [47]. Nevertheless, meloxicam has difficult in crossing the blood-brain barrier (BBB) [48].…”

Section: Discussionmentioning

confidence: 99%

Abcg2 transporter affects plasma, milk and tissue levels of meloxicam

García-Lino

Blanco-Paniagua

Astorga-Simon

et al. 2020

Biochemical Pharmacology

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ATP-binding cassette (ABCG2) is an efflux transporter that extrudes xenotoxins from cells in liver, intestine, mammary gland, brain and other organs, affecting the pharmacokinetics, brain accumulation and secretion into milk of several compounds, including antitumoral, antimicrobial and anti-inflammatory drugs. The aim of this study was to investigate whether the widely used anti-inflammatory drug meloxicam is an Abcg2 sustrate, and how this transporter affects its systemic distribution. Using polarized ABCG2-transduced cell lines, we found that meloxicam is efficiently transported by murine Abcg2 and human ABCG2. After oral administration of meloxicam, the area under the plasma concentration-time curve in Abcg2-/mice was 2-fold higher than in wild type mice (146.06 ± 10.57 µg•h/ml versus 73.80 ± 10.00 µg•h/ml). Differences in meloxicam distribution were reported for several tissues, with a 20-fold higher concentration in the brain of Abcg2-/compared to wild-type mice. Meloxicam secretion into milk was also affected by the transporter, with a 2.5-fold higher milk-to-plasma ratio in wild-type compared with Abcg2-/lactating female mice (0.58 ± 0.08 versus 0.23 ± 0.06). We conclude that Abcg2 is an important determinant of the plasma and brain distribution of meloxicam and is clearly involved in its secretion into milk.

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Section: Discussionmentioning

confidence: 99%

Abcg2 transporter affects plasma, milk and tissue levels of meloxicam

García-Lino

Blanco-Paniagua

Astorga-Simon

et al. 2020

Biochemical Pharmacology

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“…No other inflammatory drugs are described in clinical patients. Experimental studies in mice and rats showed that the NSAID meloxicam had anti-fibrotic properties in kidneys, liver, lung, and pleurisy (28–31). Glucocorticoids were not given in our patient, because wound healing could be delayed, and risk of infection can be increased.…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Pneumothorax in a Dog With Sterile Pleural Fibrosis Caused by Chylothorax

et al. 2019

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A 2-year-old, 12 kg, intact male crossbreed dog was presented with respiratory distress, exercise intolerance, and gagging. Plain thoracic radiographs revealed severe pleural effusion. Although bilateral needle thoracocentesis and chest tube placement were performed, no re-expansion of the lung lobes occurred. Pleural effusion was of chylous quality and led to lung entrapment. Computer tomography revealed a highly atrophic and atelectatic right middle lung lobe. The remaining lung lobes were only expanded to ~40%. Visceral pleura and pericardium showed a heterogeneous thickening consistent with pleural fibrosis. Partial pericardiectomy with resection of the middle lung lobe through a right lateral thoracotomy was performed. Ligation of the thoracic duct and ablation of the cisterna chyli was achieved through a single paracostal approach. Histopathology revealed chronic-active proliferative beginning granulomatous pleuritis, fibrotic pericarditis, and partial coagulative necrosis with incomplete granulomatous sequestration in the resected middle lung lobe. Chylothorax resolved after surgical intervention. Active pleural effusion resolved, and lung entrapment changed to trapped lung disease. The remaining lung lobes re-expanded to ~80% over the following 6 days. The dog was discharged 10 days later. Mild to moderate pleural effusion of non-chylic quality was present during the following 4 months. Meloxicam was administered for 4 months because of its anti-fibrotic and anti-inflammatory properties. Fifteen months later, thoracic radiographs revealed full radiologic expansion of the lungs with persistent mild pleural fibrosis. To the authors' knowledge, this is the first case report of pneumothorax due pleural fibrosis caused by chylothorax in a dog with an excellent clinical outcome.

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“…1 and Table 1 ) confirm this finding. Meloxicam is analgesic and antipyretic; has a high gastric and renal tolerance; a high therapeutic index; and preferentially inhibits COX-2 [ 31 ]. To confirm that meloxicam effectively acted as a COX-2 inhibitor at the concentrations used in our study, we evaluated if this drug could dampen the level of this enzyme, as induced by live Bb in cell lysates of primary rhesus astrocytes and microglia.…”

Section: Discussionmentioning

confidence: 99%

Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system

Ramesh

Martínez

Martin

et al. 2017

J Neuroinflammation

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BackgroundLyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), affects both the central and peripheral nervous systems. Previously, we reported that in a model of acute LNB in rhesus monkeys, treatment with the anti-inflammatory drug dexamethasone significantly reduced both pleocytosis and levels of cerebrospinal fluid (CSF) immune mediators that were induced by Bb. Dexamethasone also inhibited the formation of inflammatory, neurodegenerative, and demyelinating lesions in the brain and spinal cord of these animals. In contrast, these signs were evident in the infected animals that were left untreated or in those that were treated with meloxicam, a non-steroidal anti-inflammatory drug.MethodsTo address the differential anti-inflammatory effects of dexamethasone and meloxicam in the central nervous system (CNS), we evaluated the potential of these drugs to alter the levels of Bb-induced inflammatory mediators in culture supernatants of rhesus frontal cortex (FC) explants, primary rhesus astrocytes and microglia, and human oligodendrocytes. We also ascertained the potential of dexamethasone to modulate Bb-induced apoptosis in rhesus FC explants. As meloxicam is a known COX-2 inhibitor, we evaluated whether meloxicam altered the levels of COX-2 as induced by live Bb in cell lysates of primary rhesus astrocytes and microglia.ResultsDexamethasone but not meloxicam significantly reduced the levels of several Bb-induced immune mediators in culture supernatants of FC explants, astrocytes, microglia, and oligodendrocytes. Dexamethasone also had a protective effect on Bb-induced neuronal and oligodendrocyte apoptosis in rhesus FC explants. Further, meloxicam significantly reduced the levels of Bb-induced COX-2 in microglia, while both Bb and meloxicam were unable to alter the constitutive levels of COX-2 in astrocytes.ConclusionsThese data indicate that dexamethasone and meloxicam have differential anti-inflammatory effects on Bb-induced inflammation in glial and neuronal cells of the CNS and help explain the in vivo findings of significantly reduced inflammatory mediators in the CSF and lack of inflammatory neurodegenerative lesions in the brain and spinal cord of Bb-infected animals that were treated with dexamethasone but not meloxicam. Signaling cascades altered by dexamethasone could serve as possible therapeutic targets for limiting CNS inflammation and tissue damage in LNB.

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Meloxicam-loaded nanocapsules as an alternative to improve memory decline in an Alzheimer’s disease model in mice: involvement of Na+, K+-ATPase

Cited by 23 publications

References 60 publications

Abcg2 transporter affects plasma, milk and tissue levels of meloxicam

Abcg2 transporter affects plasma, milk and tissue levels of meloxicam

Successful Treatment of Pneumothorax in a Dog With Sterile Pleural Fibrosis Caused by Chylothorax

Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system

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