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Journal of Veterinary Internal Medicine Jul 2020Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would...
BACKGROUND
Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would provide valuable clinical and therapeutic information. The effects of meloxicam on endotoxemia have not been studied in this species.
OBJECTIVES
To study the pathophysiology and gene expression associated with experimentally induced endotoxemia, and evaluate the effects of meloxicam on experimentally induced endotoxemia in donkeys and in equine monocyte cultures.
ANIMALS
Six healthy adult female donkeys.
METHODS
Endotoxemia was induced by an IV infusion of LPS for 30 minutes. Animals either received 20 mL of saline or 0.6 mg/kg of meloxicam IV after LPS infusion. The experiments lasted 6 hours. Blood samples were collected serially for hematology, serum biochemistry, interleukin measurement, and leukocyte gene expression analysis. Vital signs were recorded throughout the study. Monocyte cultures were used to test the effects of meloxicam on LPS-activated monocytes.
RESULTS
Lipopolysaccharide induced fever, leukopenia, and neutropenia of similar magnitude in both groups, but meloxicam attenuated increases in plasma lactate, tumor necrosis factor-alpha (TNFα), and interleukin 1β concentrations compared to controls. No differences were detected between groups for cytokine mRNA expression. Furthermore, meloxicam decreased TNFα release in LPS-activated monocyte cultures.
CONCLUSIONS AND CLINICAL IMPORTANCE
Meloxicam could be a feasible option for the treatment of endotoxemia and SIRS in donkeys. Additional studies are necessary to investigate possible meloxicam-related posttranscriptional regulation and to compare this drug with other nonsteroidal anti-inflammatory drugs (NSAIDs) in animals with endotoxemia.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Endotoxemia; Equidae; Female; Interleukin-1beta; Lactic Acid; Lipopolysaccharides; Meloxicam; Monocytes; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha
PubMed: 32463537
DOI: 10.1111/jvim.15783 -
Molecules (Basel, Switzerland) Jan 2022Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the...
Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the dissolution process and influences absorption. In order to solve this problem and improve its bioavailability, we prepared it in nanocrystals with three different particle sizes to improve solubility and compare the differences between various particle sizes. The nanocrystal particle sizes were studied through dynamic light scattering (DLS) and laser scattering (LS). Transmission electron microscopy (TEM) was used to characterize the morphology of nanocrystals. The sizes of meloxicam-nanocrystals-A (MLX-NCs-A), meloxicam-nanocrystals-B (MLX-NCs-B), and meloxicam-nanocrystals-C (MLX-NCs-C) were 3.262 ± 0.016 μm, 460.2 ± 9.5 nm, and 204.9 ± 2.8 nm, respectively. Molecular simulation was used to explore the distribution and interaction energy of MLX molecules and stabilizer molecules in water. The results of differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) proved that the crystalline state did not change in the preparation process. Transport studies of the Caco-2 cell model indicated that the cumulative degree of transport would increase as the particle size decreased. Additionally, plasma concentration-time curves showed that the AUC of MLX-NCs-C were 3.58- and 2.92-fold greater than those of MLX-NCs-A and MLX-NCs-B, respectively. These results indicate that preparing MLX in nanocrystals can effectively improve the bioavailability, and the particle size of nanocrystals is an important factor in transmission and absorption.
Topics: Administration, Cutaneous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Caco-2 Cells; Calorimetry, Differential Scanning; Drug Evaluation, Preclinical; Dynamic Light Scattering; Humans; Male; Meloxicam; Microscopy, Electron, Transmission; Models, Molecular; Nanoparticles; Particle Size; Rats, Sprague-Dawley; X-Ray Diffraction; Rats
PubMed: 35056734
DOI: 10.3390/molecules27020421 -
Journal of Biomedical Materials... Aug 2021Nanostructured colloidal self-assembly (NCS) is one of the most promising drug delivery carriers in cancer treatment. The present research work aimed towards...
Nanostructured colloidal self-assembly (NCS) is one of the most promising drug delivery carriers in cancer treatment. The present research work aimed towards synthesizing meloxicam (MLX) loaded NCS for its improved circulation half-life and increased cellular internalization. NCS was formulated using glyceryl monoolein, Pluronic® F127, and MLX. Quality by Design experiments with a quadratic model was subjected to optimization of the formulation. The optimized NCS with an average particle size of 185.5 ± 3.02 nm showed higher MLX encapsulation (94.74 ± 3.41%) and sustained release behavior of MLX up to 24 hr. in vitro cytotoxicity of the developed NCS with MCF-7 and MDA-MB-231 cell lines confirmed lower cell viability and a higher rate of cell growth inhibition. This MLX loaded NCS showed dual activity as an antitumor and anti-inflammatory in highly invasive estrogen-dependent MDA-MB-231 cells due to the high expression of cyclooxygenase-2 (COX-2). Besides, an activity of the MLX-NCS was also observed in 3D printed MCF-7 cells. This investigation shows the possible use of MLX-NCS as an efficient cancer drug delivery system with excellent colloidal stability, sustained release of MLX, enhanced antitumor and anti-inflammatory efficacy in 3D printed scaffolds. In contrast to toxicity study in 2D culture, the 3D constructs revealed the activity of the MLX via COX-2 independent mechanism and demonstrated that the relationship between COX-2 expression and antitumor activity of inhibitors is limited. In conclusion, the overall observations and results of this study strengthen the hypothesized development of NCS as a next-generation therapeutics regimen for cancer therapy.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Breast Neoplasms; Colloids; Cyclooxygenase 2 Inhibitors; Drug Carriers; Female; Humans; MCF-7 Cells; Meloxicam; Nanostructures; Printing, Three-Dimensional
PubMed: 33289225
DOI: 10.1002/jbm.a.37135 -
Clinical Pharmacology in Drug... Jan 2022Meloxicam is an enolate nonsteroidal anti-inflammatory agent. This trial investigated the pharmacokinetics, safety, and bioequivalence of single oral doses of Aomei... (Randomized Controlled Trial)
Randomized Controlled Trial
Pharmacokinetics of Meloxicam Tablets in Healthy Chinese Adults in the Fasting and Fed States: A Single-Site, Single-Dose, Randomized, Open, 2-Period, 2-Sequence, Crossover Bioequivalence Study.
Meloxicam is an enolate nonsteroidal anti-inflammatory agent. This trial investigated the pharmacokinetics, safety, and bioequivalence of single oral doses of Aomei meloxicam (15 mg) and Mobic meloxicam (15 mg) in healthy volunteers under fasting and fed conditions. A single-site, single-dose, randomized, open, 2-period, 2-sequence, crossover bioequivalence study was performed: 24 healthy volunteers were enrolled in each of the fasting and fed arms. Each HV was randomly assigned to receive the Aomei drug (test) in one period and the Mobic drug (reference) in the other period. The concentration of meloxicam in plasma was detected using liquid chromatography-tandem mass spectrometry. The primary pharmacokinetic parameters were calculated using a noncompartmental model. In the fasting arm, the 90% confidence interval of the geometric mean ratios of maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable plasma concentration, and area under the concentration-time curve from time 0 to infinity between the test and reference products were 99.5% to 111.7%, 101.2% to 106.8%, and 101.8% to 108.3%, respectively. In the fed arm, the 3 parameters were 94.1% to 102.4%, 97.6% to 103.0%, and 97.5% to 103.7%, respectively. These parameters were in the range of 80% to 125%, and the 2 products were considered bioequivalent in both the fasting and fed states and were well tolerated. The severity of all adverse events was mild. Aomei meloxicam tablets and Mobic meloxicam tablets were bioequivalent in healthy Chinese volunteers.
Topics: Adult; China; Cross-Over Studies; Fasting; Humans; Meloxicam; Tablets; Therapeutic Equivalency
PubMed: 34137514
DOI: 10.1002/cpdd.965 -
Journal of Zoo and Wildlife Medicine :... Mar 2023Fish species are important for various purposes including aquaculture stock and display animals, but there are significant gaps in the medical knowledge regarding...
Fish species are important for various purposes including aquaculture stock and display animals, but there are significant gaps in the medical knowledge regarding pharmacological parameters and effective pain management. Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has been studied in few teleost species and with several administration routes. However, these species were typically freshwater or euryhaline fish, and evaluation in marine species is lacking. The pharmacokinetic properties of meloxicam were determined in nine adult China rockfish (), presumed healthy based on physical examination and benign medical histories. Based on a pilot study, China rockfish were given 1 mg/kg meloxicam via IM injection in the epaxial musculature, and, after a 48-h washout period, 1 mg/kg meloxicam was given by PO gavage. Blood samples were collected from the caudal vein at baseline and at nine time intervals over a 48-h time period following administration of meloxicam. Plasma meloxicam concentrations were determined by reverse phase high-performance liquid chromatography, and noncompartmental analysis was performed. The mean peak plasma concentration after IM injection was 4.9 µg/ml, and the mean terminal half-life was 5.0 h. The mean peak plasma concentration after PO administration was 0.07 µg/ml. Based on these findings, IM injected meloxicam reaches plasma levels consistent with therapeutic concentrations in select mammals, and peak levels were maintained for ≤12 h. Single-dose PO administration failed to achieve similar concentrations, and clinical practicality is unknown. Further studies evaluating NSAID multidose regimes and their pharmacodynamic effects may provide additional dosing information.
Topics: Animals; Meloxicam; Pilot Projects; Thiazines; Thiazoles; Half-Life; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Administration, Oral; Injections, Intramuscular; Perciformes; China; Mammals
PubMed: 36971623
DOI: 10.1638/2022-0080 -
Journal of Investigational Allergology... 2006Anaphylactic reaction to meloxicam has never been reported to date. We report 2 cases of meloxicam-induced anaphylactic reaction with no sensitivity to another selective...
Anaphylactic reaction to meloxicam has never been reported to date. We report 2 cases of meloxicam-induced anaphylactic reaction with no sensitivity to another selective cyclooxygenase 2 inhibitor. A thorough drug allergy work-up should be done before other cyclooxygenase inhibitors are prescribed.
Topics: Adult; Anaphylaxis; Cyclooxygenase 2 Inhibitors; Female; Humans; Meloxicam; Thiazines; Thiazoles
PubMed: 17039673
DOI: No ID Found -
Molecular Neurobiology Jan 2023Neuronal apoptosis is considered to be a critical cause of Alzheimer's disease (AD). Recently, meloxicam has shown neuroprotective effects; however, the inherent...
Meloxicam Inhibits Apoptosis in Neurons by Deactivating Tumor Necrosis Factor Receptor Superfamily Member 25, Leading to the Decreased Cleavage of DNA Fragmentation Factor Subunit α in Alzheimer's Disease.
Neuronal apoptosis is considered to be a critical cause of Alzheimer's disease (AD). Recently, meloxicam has shown neuroprotective effects; however, the inherent mechanisms are highly overlooked. Using APP/PS1 transgenic (Tg) mice as in vivo animal models, we found that meloxicam inhibits apoptosis in neurons by deactivating tumor necrosis factor receptor superfamily member 25 (TNFRSF25), leading to the suppression of the expression of fas-associated protein with death domain (FADD) and the cleavage of DNA fragmentation factor subunit α (DFFA) and cysteine aspartic acid protease-3 (caspase 3) via β-amyloid protein (Aβ)-depressing mechanisms. Moreover, the meloxicam treatment blocked the effects of β-amyloid protein oligomers (Aβo) on stimulating the synthesis of tumor necrosis factor α (TNF-α) and TNF-like ligand 1A (TL1A) in neuroblastoma (N) 2a cells. TNF-α and TL1A induce apoptosis in neurons via TNFR- and TNFRSF25-dependent caspase 3-activating mechanisms, respectively. Knocking down the expression of TNFRSF25 blocked the effects of TL1A on inducing apoptosis in neurons by deactivating the signaling cascades of FADD, caspase 3, and DFFA. Consistently, TNFRSF25 shRNA blocked the effects of Aβo on inducing neuronal apoptosis, which was corroborated by the efficacy of meloxicam in inhibiting Aβo-induced neuronal apoptosis. By ameliorating neuronal apoptosis, meloxicam improved memory loss in APP/PS1 Tg mice.
Topics: Animals; Mice; Alzheimer Disease; Amyloid beta-Peptides; Apoptosis; Caspase 3; DNA Fragmentation; Meloxicam; Mice, Transgenic; Neurons; Tumor Necrosis Factor-alpha; Receptors, Tumor Necrosis Factor, Member 25
PubMed: 36279100
DOI: 10.1007/s12035-022-03091-z -
Journal of the American Association For... Jan 2022The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg...
The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg once daily and carprofen at 5-10 mg/kg twice daily may not be adequate to provide analgesia in mice. Several studies have suggested that doses up to 20 mg/kg of meloxicam and carprofen are needed to provide analgesic efficacy. This study investigated the clinical safety of these higher doses of meloxicam and carprofen by evaluating their potential for renal and gastrointestinal toxicity. Female CD-1 mice were given 20 mg/kg of either meloxicam, carprofen, or an equivalent volume of saline subcutaneously once daily for 3 or 7 d. On day 4, mice treated for 3 d were euthanized, and on days 8 and 15, mice treated for 7 d were euthanized. Blood was collected by cardiocentesis for serum chemistry analysis. Feces was collected from the colon for fecal occult blood testing, and tissues were collected for histopathology. No clinically significant changes in serum chemistry profiles were found in the drug-treated mice at any time point as compared with the saline controls. Fecal occult blood and histologic evidence of gastritis was associated with meloxicam administration in mice evaluated at days 4 and 8. By day 15, there was no association with meloxicam treatment and the presence of fecal occult blood or gastritis. There was no association between fecal occult blood and gastritis in the carprofen or saline-treated mice regardless of the treatment durations. These findings suggest that 20 mg/kg of meloxicam in mice causes gastric toxicity when given for 3 or 7 d and should be used cautiously; however, carprofen at 20 mg/kg appears to have minimal toxic effects with regard to the parameters measured.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Female; Meloxicam; Mice; Thiazines; Thiazoles
PubMed: 34920791
DOI: 10.30802/AALAS-JAALAS-21-000071 -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2021The influence of different chromatographic conditions and the process of spot visualization on determining the limit of detection as well as quantification (LOD and LOQ)...
The influence of different chromatographic conditions and the process of spot visualization on determining the limit of detection as well as quantification (LOD and LOQ) of meloxicam by TLC-densitometric technique was estimated. Of all chromatographic conditions tested, the lowest limiting values, thus the best sensitivity, in the NP-TLC system was achieved on silica gel 60F254 and neutral aluminum oxide plates developed with the mobile phase consisting of ethyl acetate/toluene/n-butylamine (2:2:1, V/V/V). In the case of the RP-TLC method, a mixture of methanol/water (8:2, V/V) enabled densitometric detection of meloxicam at the lowest concentration level on RP-8F254 and RP-18F254 plates. Additionally, the smallest LOD value of meloxicam ensured crystalline violet and gentian violet as visualization agents on silica gel 60F254 and neutral aluminum oxide 150F254 plates, resp. Comparison of the densitometrically obtained spectra of meloxicam drug and its standard after the use of appropriate visualization agents could be a good and cheap alternative tool for the identification of meloxicam as an active pharmaceutical ingredient.
Topics: Chromatography, Thin Layer; Cost-Benefit Analysis; Densitometry; Indicators and Reagents; Limit of Detection; Meloxicam; Reference Standards; Reproducibility of Results
PubMed: 32697743
DOI: 10.2478/acph-2021-0006 -
Veterinary Medicine and Science Sep 2023Fish in aquatic environments are end consumers of the food chain and are widely used for the evolution effects of environmental pollution and their interactions in...
BACKGROUND
Fish in aquatic environments are end consumers of the food chain and are widely used for the evolution effects of environmental pollution and their interactions in aquatic ecosystem.
OBJECTIVE
In the present study, common carp (Cyprinus carpio) fingerlings were selected to assess the potential risk and aquatic toxicity of meloxicam as a non-steroidal anti-inflammatory and a commonly used pharmaceutical drug.
METHODS
In order to evaluate meloxicam toxicological effect on haematological, antioxidant status, enzymological and histological parameters, based on its LC50 24 h acute toxicity (10.05 mg L ), fish fingerlings were exposed to four doses of meloxicam including; 0 (control), 0.1 (low), 1 (medium) and 2 mg L (high) under static bioassay method for 28 days.
RESULTS
The results showed that sublethal doses of meloxicam significantly decreased alanine aminotransferase, alkaline phosphatase, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels in comparison with the control group after 28 days (p < 0.05). However, red blood cell, haematocrit, haemoglobin and malondialdehyde values in fish exposed to meloxicam significantly increased alongside its concentration (p < 0.05) more than the control group after 28 days. SOD, CAT and GPX mRNA expression levels in gill, liver, kidney and brain organ of fish under meloxicam treatment were significantly down-regulated compared to the control group (p < 0.05). Histopathological assessment showed the increased vacuolation in hepatocytes in liver of fish exposure to medium and high doses of meloxicam.
CONCLUSION
In conclusion, meloxicam induces oxidative stress in common carp which results a disruption of physiological and health status of this species based on our current findings.
Topics: Animals; Antioxidants; Meloxicam; Carps; Ecosystem; Anti-Inflammatory Agents, Non-Steroidal; Glutathione Peroxidase
PubMed: 37616188
DOI: 10.1002/vms3.1207